Israel Medical Association Journal

Recent studies using propensity score matching have clearly indicated that contrast nephropathy following computed tomography occurs in hospitalized patients with advanced chronic kidney disease (eGFR < 30 ml/min/1.73 m²) and that this iatrogenic complication is likely underestimated because of concomitant renal functional recovery, unrelated to the imaging procedure. These findings should be considered regarding contrast-enhanced studies in such patients.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.

Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.

Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.

Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.

Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Background: Holocaust survivors report a much higher prevalence of osteoporosis and fracture in the hip joint compared to those who were not Holocaust survivors.

Objective: To evaluate whether being a Holocaust survivor could affect the functional outcome of hip fracture in patients 64 years of age and older undergoing rehabilitation.

Methods: A retrospective cohort study compromising 140 consecutive hip fracture patients was conducted in a geriatric and rehabilitation department of a university-affiliated hospital. Being a Holocaust survivor was based on registry data. Functional outcome was assessed by the Functional Independence Measure (FIM)TM at admission and discharge from the rehabilitation ward. Data were analyzed by t-test, chi-square test, and linear regression analysis. 

Results: Total and motor FIM scores at admission (P = 0.004 and P = 0.006, respectively) and total and motor FIM gain scores at discharge (P = 0.008 and P = 0.004 respectively) were significantly higher in non-Holocaust survivors compared with Holocaust survivors. A linear regression analysis showed that being a Holocaust survivor was predictive of lower total FIM scores at discharge (β = -0.17, P = 0.004).

Conclusion: Hip fracture in Holocaust survivors showed lower total, motor FIM and gain scores at discharge compared to non-Holocaust survivor patients. These results suggest that being a Holocaust survivor could adversely affect the rehabilitation outcome following fracture of the hip and internal fixation. 

 

Objectives: To investigate current smoking trends among Israeli physicians.

Methods: All practicing physicians at a tertiary university-affiliated medical center in central Israel were invited to complete a Web-based questionnaire on smoking habits and smoking-related issues via the institutional email. Findings were compared to those in the general population and between subgroups.

Results: Of the 90 responders (53 male, 88 Jewish), 54 (60%) had never smoked, 21 (23.3%) were past smokers, and 15 (16.7%) were current smokers. The rate of current smokers was lower than in the general population. The proportion of current smokers was higher among residents than attending physicians and among physicians in surgical compared to medical specialties. Past smokers accounted for 17.9% of the residents (average age at quitting 26.2 years) and 28.1% of the attending physicians (average age at quitting 33.0 years). Non-smokers more frequently supported harsh anti-smoking legislation.

Conclusions: The rate of smoking is lower in physicians than in the general population but has not changed over the last 15 years. Anti-smoking programs should particularly target physicians in surgical specialties. 

Background: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline.

Objectives: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD.

Methods: The study group included 113 newly referred ADHD children aged 5–15 years (mean age 8.8 ± 2.7).

Results: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 45 (41%). There was a very low inverse statistical correlation between scores on Conners’ Rating Scale and ferritin levels, probably without clinical significance. 

Conclusions: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.