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.

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: 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: 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.

Objectives: To report 3 years national experience with orthotopic liver transplantation, and to evaluate patient and perioperative risk factors that could affect 1 year graft survival.

Methods: The study related to all 124 isolated adult liver transplantations performed in Israel between October 1997 and October 2000. Data were abstracted from the medical records. One-year graft survival was described using the Kaplan-Meier survival curve and three multivariate logistic regression models were performed: one with preoperative case-mix factors alone, and the other two with the addition of donor and operative factors respectively.

Results: Of the 124 liver transplantations performed, 32 failed (25.8%). The 1 year survival was lower than rates reported from both the United States and Europe, but the difference was not significant. Of the preoperative risk factors, recipient age ≥ 60 years, critical condition prior to surgery, high serum bilirubin and serum hemoglobin ≤ 10 g/dl were independently associated with graft failure, adjusting for all the other factors that entered the logistic regression equation. Extending the model to include donor and operative factors raised the C-statistic from 0.79 to 0.87. Donor age ≥ 40, cold ischemic time > 10 hours and a prolonged operation (> 10 hours) were the additional predictors for graft survival. A MELD score of over 18 was associated with a sixfold increased risk for graft failure (odds ratio = 6.5, P = 0.001).

Conclusions: Graft survival in Israel is slightly lower than that reported from the U.S. and Europe. Adding donor and operative factors to recipient characteristics significantly increased our understanding of 1 year survival of liver grafts.

Objectives: To describe and analyze how PCPs[1] in the IDF[2] view their roles as primary care providers and to characterize how they perceive the quality of the medical care that they provide.

Methods: We conducted a survey using a questionnaire that was mailed or faxed to a representative sample of PCPs. The questionnaire included demographic background, professional background, statements on self-perception issues, and ranking of roles as a PCP in the IDF.

Results: Statements concerning commitment to the patient were ranked higher than statements concerning commitment to the military organization. Most physicians perceive the quality of the medical care service that they provide as high; they also stated that they do not receive adequate continuous medical education.

Conclusions: Our survey shows that PCPs in the IDF, like civilian family physicians, perceive their primary obligation as serving the needs of their patients but are yet to take on the full role of “gatekeepers” in the IDF’s healthcare system. We conclude that the Medical Corps should implement appropriate steps to ensure that PCPs are prepared to take on a more prominent role as “gatekeepers” and providers of high quality primary medical care.

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[1] PCP = primary care physician

[2] IDF = Israel Defense Force

Background: Oral contraceptive users are at increased risk for both arterial and venous thrombosis, some of which can be fatal. Studies are consistent with the existence of a synergism between cigarette smoking and OC[1] use in the pathogenesis of myocardial infarction in young women.

Objectives: To study the relationship between OC use, cigarette smoking and other cardiovascular risk factors among young women.

Methods: A systematic sample of military personnel, upon discharge from service in the Israel Defense Forces, was asked to complete a research questionnaire. Body weight and height were measured and body mass index computed.

Results: Overall, 16,258 questionnaires were collected and analyzed during this 20 year study. There was a gradual, significant increase in OC use until the mid-1980s, from approximately 45% to 60% (P < 0.001), followed by steady rates of 58–64% since then. In contrast, the rates of smoking decreased significantly in the mid-1980s, from approximately 42% to a nadir of 22% in 1991. Since then, the rate of smoking has increased slowly but steadily, to reach a level of 35% in 1999. The OC users were more often of western (Ashkenazi) origin and came from families with more education and fewer siblings. They were more often smokers than non-OC users, and started smoking at a younger age. They had significantly lower BMI[2] than non-users. OC use was nearly identical in groups with or without multiple cardiovascular risk factors (smoking, obesity, family history).

Conclusions: Smoking and OC use are strongly associated. Other cardiovascular risk factors (smoking, obesity, family history) do not prevent OC users from smoking or smokers to use OC. We suggest that primary care physicians discourage smoking among adolescent females who wish to start using OC. A thorough medical history should be obtained to recognize all risk factors for cardiovascular disease and to provide for appropriate contraception counseling.

Background: Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants.

Objective: To retrospectively analyze data obtained on infants with severe IVH[1] in relation to blood K⁺ concentrations.

Methods: We identified all patients with severe IVH born between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (±1 week) without IVH in terms of head ultrasound findings on day 5, and whole blood K⁺ on days 3–5.

Results: There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K⁺ than the control group. Blood pH and K⁺ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K⁺ and IVH status.

Conclusions: Severe IVH is significantly associated with higher blood K⁺ concentrations. A causal relationship cannot be ascertained at this point.