Israel Medical Association Journal

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.

Artificial Intelligence (AI), particularly large language models (LLMs) like OpenAI's ChatGPT, has shown potential in various medical fields, including pediatrics. We evaluated the utility and integration of LLMs in pediatric medicine. We conducted a search in PubMed using specific keywords related to LLMs and pediatric care. Studies were included if they assessed LLMs in pediatric settings, were published in English, peer-reviewed, and reported measurable outcomes. Sixteen studies spanning pediatric sub-specialties such as ophthalmology, cardiology, otology, and emergency medicine were analyzed. The findings indicate that LLMs provide valuable diagnostic support and information management. However, their performance varied, with limitations in complex clinical scenarios and decision-making. Despite excelling in tasks requiring data summarization and basic information delivery, the effectiveness of the models in nuanced clinical decision-making was restricted. LLMs, including ChatGPT, show promise in enhancing pediatric medical care but exhibit inconsistent performance in complex clinical situations. This finding underscores the importance of continuous human oversight. Future integration of LLMs into clinical practice should be approached with caution to ensure they supplement, rather than supplant, expert medical judgment.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by an inadequate attenuation of the cytotoxic and innate immune system resulting in uncontrolled inflammation in multiple organ systems. Predominant clinical findings include fever, cytopenia, and hepatosplenomegaly [1].

Infectious diseases are a well-documented trigger of HLH, with viral infection being the most common cause. Less commonly, HLH has also been reported in the setting of bacterial infections, with rare cases described secondary to rickettsial diseases [1]. In this report, we present a case of HLH in the setting of bacterial infection with Rickettsia typhi, murine typhus.

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.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Background: Guidelines for pandemic preparedness emphasize the role of sentinel and syndromic surveillance in monitoring pandemic spread.

Objectives: To examine advantages and obstacles of utilizing a sentinel influenza surveillance system to monitor community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity based on Israel's experience from mid-March to mid-May 2020.

Methods: Several modifications were applied to the influenza surveillance system. The clinical component relied mainly on pneumonia and upper respiratory infection (URI) consultations with primary care physicians as well as visits to emergency departments (ED) due to pneumonia. The virological data were based on nasopharyngeal swabs obtained from symptomatic patients who visited outpatient clinics.

Results: By week 12 of the pandemic, the crude and age-specific primary physician consultation rates due to URI and pneumonia declined below the expected level, reaching nadir that lasted from week 15 until week 20. Similarly, ED visits due to pneumonia were significantly lower than expected from weeks 14 and 15 to week 20. The virological surveillance started on week 13 with 6/253 of the swabs (2.3%) positive for SARS-CoV-2. There was a peak of 13/225 positive swabs on week 145.8%. During weeks 17–20, none of the swabs (47–97 per week) were positive for SARS-CoV-2. This trend was similar to national data.

Conclusions: The virological component of the surveillance system showed the SARS-CoV-2 community spread, but had low sensitivity when virus activity was low. The clinical component, however, had no yield. Sentinel surveillance can assist in monitoring future novel pandemics and should be augmented in revised preparedness plans.

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

Background: Nebulized hypertonic saline (HS) treatment is unavailable to large populations worldwide.

Objectives: To determine the bacterial contamination and electrolyte concentrations in homemade (HM-HS) vs. pharmacy made (PM-HS).

Methods: We conducted three double-blind consecutive trials: 50 boiled-water homemade 3%-HS (B-HM-HS) bottles and 50 PM-HS. The bottles were cultured after 48 hours. Electrolyte concentrations were measured in 10 bottles (5 per group). Forty bottles (20 per group) were distributed to volunteers for simulation of realistic treatment by drawing 4 ml HS three times daily. From each bottle, 4 ml samples were cultured after 1, 5, and 7 days. Volunteers prepared 108 bottles containing 3%-HS, sterilizing them using a microwave oven (1100–1850W). These bottles were cultured 24 hours, 48 hours, and 1 month after preparation.

Results: Contamination rates of B-HM-HS and PM-HS after 48 hours were 56% and 14%, respectively (P = 0.008). Electrolyte concentrations were similar: 3.7% ± 0.4 and 3.5% ± 0.3, respectively (P = NS). Following a single day of simulation B-HM-HS bottles were significantly more contaminated than PM-HS bottles: 75% vs. 20%, respectively (P < 0.01). By day 7, 85% of PM-HS bottles and 100% of B-HM-HS bottles were contaminated (P = 0.23). All 108 microwave-oven prepared bottles (MICRO-HS) were sterile, which was significantly better than the contamination rate of B-HM-HS and PM-HS (P < 0.001). Calculated risk for a consecutive MICRO-HS to be infected was negligible.

Conclusion: Microwave preparation provides sterile HS with adequate electrolyte concentrations, and is a cheap, fast, and widely available method to prepare HS.

Background: Israel is a country with a sunny climate; however, vitamin D deficiency and insufficiency are common findings in certain populations whose exposure to sunlight is limited. Medical residency is known for long indoor working hours, thus theoretically limiting the opportunities for sun exposure.

Objectives: To evaluate whether the vitamin D status among residents in a single medical center in Tel Aviv is below the normal range.

Methods: Forty-six residents (28 females, 18 males, average age 33.9 ± 2.8 years) in three residency programs (internal medicine, general surgery/obstetrics and gynecology, pediatrics) were recruited. Demographic data, personal lifestyle, physical activity details and sun exposure duration were obtained by a questionnaire. Serum levels for 25(OH)D were analyzed by a radioimmunoassay.

Results: The mean serum 25(OH)D concentration was 29.8 ± 5.8 ng/ml. According to Institute of Medicine definitions, none of the residents were vitamin D deficient and only two residents (4%) were vitamin D insufficient (15 ng/ml each). The level of 25(OH)D was similar among the various medical specialties. The 25(OH)D levels correlated with the duration of sun exposure and the number of offspring (regression analysis: R2 = 9.2%, P < 0.04 and R2 = 8.9%, P < 0.04, respectively), but not with nutritional data, blood chemistry, or extent of physical activity. 

Conclusions: Most of the residents maintained normal or near normal 25(OH)D levels, indicating that the residency program itself did not pose a significant risk for vitamin D deficiency. 

 

Background: Selection of appropriate reference charts for fetal biometry is mandatory to ensure an accurate diagnosis. Most hospitals and clinics in Israel use growth curves from the United States. Charts developed in different populations do not perform well in the Israeli population.

Objectives: To construct new reference charts for fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), using a large sample of fetuses examined at 14–42 weeks gestational age in a medical center and a community ultrasound unit located in two different regions of Israel. 

Methods: Data from the medical center and the community clinic were pooled. The mean and standard error of each measure for each week was calculated. Based on these, reference charts were calculated using quantiles of the normal distribution. The performance of the reference charts was assessed by comparing the new values to empirical quantiles.

Results: Biometric measurements were obtained for 79,328 fetuses. Growth charts were established based on these measurements. The overall performance of the curves was very good, with only a few exceptions among the higher quantiles in the third trimester in the medical center subsample.

Conclusions: We present new local reference charts for fetal biometry, derived from a large and minimally selected Israeli population. We suggest using these new charts in routine daily obstetric practice.

 

Background: Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation.

Objectives: To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation.

Methods: We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2–6 months. Milk was collected by manual expression in mid-breastfeeding.

Results: The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C12 and C14) decreased significantly over time. In contrast, C12:0 and C14:0 combined increased significantly during lactation (R2 = 10.0%, P < 0.03).

Conclusions: Women who lactated for more than 1 year had higher C12 and C14 FA percentages in their milk than women who lactated for 2–6 months.

Background: Major advances in the treatment of perinatal asphyxial–hypoxic ischemic encephalopathy followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care.

Objectives: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE[1] in what we believe is the first report on non-experimental hypothermia for PA-HIE from Israel.

Methods: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008–2009.

Results: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5ºC) was begun at a median age of 4.2 hours of life (range 2.5–6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental follow-up of the five surviving infants at median age 7.2 months (4.1–18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures.

Conclusions: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

Background: A survey conducted among Israel Defense Force primary care physicians in 2001 revealed that they consider patients' needs more than they do organizational needs and that the education PCPs[1] currently receive is inadequate. In 2003 the medical corps initiated a multi-format continuous medical education program aimed at improving skills in primary care medicine.

Objectives: To measure and analyze the effect of the tailored-made CME[2] program on PCPs’ self-perception 3 years after its implementation and correlate it to clinical performance.

Methods: In 2006 a questionnaire was delivered to a representative sample of PCPs in the IDF[3]. The questionnaire included items on demographic and professional background, statements on self-perception issues, and ranking of roles. We compared the follow-up survey (2006) to the results of the original study (2001) and correlated the survey results with clinical performance as measured through objective indicators.

Results: In the 2006 follow-up survey PCPs scored higher on questions dealing with their perception of themselves as case managers (3.8 compared to 4.0 on the 2001 survey on a 5 point scale, P = 0.046), perceived quality of care and education (3.5 vs. 3.8, P = 0.06), and on questions dealing with organizational commitment (3.5 vs. 3.8, P=0.01). PCPs received higher scores on clinical indicators in the later study (odds ratio 2.05, P < 0.001).

Conclusions: PCPs in the IDF perceive themselves more as case managers as compared to the 2001 survey. A tailor-made CME program may have contributed to the improvement in skills and quality of care.