Israel Medical Association Journal

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: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Background: The increasing use of micromobility solutions (MMS), including electric scooters, electric, and non-motorized bicycles, has revolutionized urban transportation. We addressed the rising incidence of injuries related to pedestrian-MMS accidents, with a specific focus on pedestrian injuries.

Objectives: To improve clinician comprehension of patient characteristics and injuries associated with pedestrian-MMS accidents and to provide insights for injury prevention, policy making, and urban planning.

Methods: We conducted a retrospective analysis, June 2017 to January 2023, of pedestrians who were admitted to the emergency department post-MMS accidents. Data included patient characteristics, type of MMS, time of the accident, and outcome variables including type of injury, hospitalization, and surgical treatment.

Results: The study cohort included 498 pedestrians (57.7% women), with a mean age of 42.3 ± 21.8 years. Nighttime accidents were 53.2% of cases. Fractures were the dominant type of injury (18.3% of the total cohort). Age, particularly those ≥ 60 years, significantly (P < 0.05) influenced fracture, hospitalization, and surgery rates (30.6%, 22.4%, and 12.6%, respectively). The odds ratio of having a fracture for pedestrians ≥ 60 years was 5.35 (P = 0.008). Interestingly, the type of MMS did not significantly affect outcomes.

Conclusions: Age emerged as a critical factor in injury severity, emphasizing the need for age-specific safety measures in urban environments. The type of MMS did not show a significant influence on outcomes, emphasizing the importance of a comprehensive regulation of all MMS types. The high rate of accidents during nighttime calls for focused interventions during this period to prevent accidents.

Minocycline is a tetracycline antibiotic prescribed to treat various infections, acne vulgaris, and rosacea. In addition to its antibiotic activity, it possesses anti-inflammatory properties, including reducing the production of proinflammatory cytokines, suppressing neutrophil chemotaxis, activating superoxide dismutase, and inhibiting phagocytosis. Among its side effects are hypersensitivity syndrome reactions, drug-induced lupus, and polyarteritis nodosa (PAN) [1].

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

Postmortem sperm retrieval allows for the procreation of biological children using the sperm of a deceased male; however, the data on how to optimize this procedure and its potential long-term effect are limited. We searched medical databases (PUBMED and Cochrane) and performed a systematic review of articles published from the databases' inception until December 2023. Case reports, case studies, and reviews reporting on and investigating the methodology and outcome of postmortem sperm retrieval were included. The primary search yielded 98 publications. After assessing eligibility and evaluating with a quality assessment tool, 17 articles remained, including 11 single case reports and 6 case series. Overall, 103 clinical cases of posthumous sperm retrieval were identified, and eight deliveries were reported. Most publications lacked information regarding the conditions to which the bodies were exposed before postmortem sperm retrieval. Moreover, sperm viability assessment was not performed routinely, and there was no examination of the potential genetic and epigenetic damage that may have occurred. Currently, there is a lack of standardization for postmortem sperm retrieval procedures. The lack of specific information regarding the potential hypoxic damage to the viable sperm cells may limit the safety of using these cells for procreation. These gaps in our current knowledge are relevant and should be expressed in the informed consent given to the potential users.

Pediatrics stands at the forefront of medical innovation, from neonatal care to the management of complex acute and chronic conditions. The field continues to evolve, driven by pioneering research. Advances in genetics, technology, and personalized medicine are transforming pediatric care, addressing the diverse needs of children globally, and offering new opportunities to enhance health outcomes and quality of life.

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Background: Chest radiograph is a standard procedure for diagnosis of pneumonia; however, interpretation shows considerable variability among observers.

Objectives: To assess the extent of agreement between pediatric residents and board-certified radiologists in interpretation of chest radiography for detection of pneumonia. To evaluate the impact of resident experience, patient age, and signs of infection on this phenomenon.

Methods: The cohort included 935 patients with suspected pneumonia admitted to the pediatric emergency department at a non-tertiary medical center in Israel 2019–2021. All patients had chest radiographs interpreted by a resident and a radiologist. Interobserver agreement was assessed using Κ and prevalence-adjusted bias-adjusted κ (PABAK) with 95% confidence intervals (95%CI). Results were stratified by resident experience (junior or senior), patient age (≤ 3 vs. > 3 years), white blood cells (≤ 15,000 vs. > 15,000 cells/ml), C-reactive protein (≤ 5 vs. > 5.0 mg/dl), and temperature (< 38.0°C vs. ≥ 38.0°C).

Results: Moderate agreement between pediatric residents and radiologists was demonstrated for diagnosis of pneumonia (κ= 0.45). After adjustment for disease prevalence, the extent of agreement increased to near-substantial (PABAK= 0.59, 95% confidence interval 0.54–0.64). The extent of agreement was higher for children over 3 years of age and in patients without clinical or biochemical features of pneumonia, especially when diagnosis of pneumonia was ruled out.

Conclusions: A second reading of chest radiographs by an experienced radiologist should be considered, particularly for patients younger than 3 years of age and in those with signs of infection and an initial diagnosis of pneumonia.

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.

Anorexia nervosa (AN) is a common psychiatric disorder primarily affecting adolescents and young adults. It is characterized by extreme restriction of food intake, distorted body image, and weight-gain anxiety. We report a case with rapid progression and severe metabolic changes in a young restrictive-type AN patient, highlighting unique aspects of this presentation and discussing pathophysiology.

An 11-year-old girl presented with a significant 29% weight loss over 4 months, leading to a body mass index (BMI) of 11.7 (< 1st BMI percentile for her sex and age). She presented with severe bradycardia and metabolic abnormalities including hypoglycemia, hypercholesterolemia, and hypothyroidism. Following diagnosis with restrictive type AN based on the DSM-5 [1] criteria and stabilization at our department, she was transferred to a specialized unit. The hypercholesterolemia our patient presented with is more typical of binge-eating/purging subtype AN, yet it was markedly elevated in this restrictive-type case.

Inborn errors of immunity (IEI), formerly known as primary immunodeficiencies (PID), comprise a diverse group of genetic disorders characterized by increased susceptibility to infections, autoimmunity, autoinflammatory conditions, allergies, and malignancies. These disorders exhibit a broad spectrum of clinical manifestations, including extra-hematopoietic manifestations, which may also present later in life. IEI diagnosis has significantly advanced, in line with the common use of next-generation sequencing-based genetic platforms, such as whole-exome and whole-genome sequencing. Treatment approaches have evolved beyond infection management to include curative therapies such as hematopoietic stem cell transplantation, gene therapy, and targeted pharmacologic treatments. In this review, we explore recent advancements in the understanding, diagnosis, and treatment of IEI, emphasizing the rapid progress in this expanding field.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness with broad spectrum of clinical manifestations ranging from asymptomatic cases to severe complications such as acute respiratory failure, multi-organ dysfunction, and death.

Objectives: To evaluate the platelet-lymphocyte ratio (PLR) as a marker of disease severity and mortality in COVID-19 patients. To explore the relationship between PLR and other inflammatory indicators, specifically C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR).

Methods: The cohort included 400 patients (206 males, 194 females; mean age: 64.5 ± 17.1 years [range 20–100 years]) who were hospitalized between April 2020 and December 2021. Data were collected on demographic and clinical characteristics, including ward and critical care details. CRP, NLR, and PLR values were recorded on the first and last days of hospitalization. Patients were categorized based on their hospitalization outcomes.

Results: PLR statistically increased during hospitalization, from 245 ± 160 at admission to 341 ± 747 at discharge (P < 0.001). A significant association was found between PLR and both the length of hospital stay and mortality. The mean PLR in the deceased group was 445 ± 590, compared to 304 ± 795 in the survivors, P = 0.007. This finding showed a correlation between higher PLR and increased severity and mortality.

Conclusion: PLR has been identified as a relevant marker for assessing the severity of COVID-19. Elevated PLR levels are associated with cytokine storm, length of hospital stay, and mortality. The results highlight the relationship between elevated PLR and poor outcome in COVID‐19 patients, suggesting its use in monitoring disease progression and prognosis.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.