Israel Medical Association Journal

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.

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].

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.

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.

Background: Immunoglobulin 4 (IgG4) is the least abundant immunoglobulin in the sera of healthy individuals; however, its levels can vary in different diseases such as IgG4-related disease (high) or Sjögren's syndrome (low). While previous studies have suggested the importance of IgG4 in autoimmune diseases, the clinical and biological significance of high or low levels remains unclear.

Objectives: To investigate the association between IgG4 antibody levels and systemic sclerosis (SSc), as well as the clinical features of the disease.

Methods: We measured IgG4 levels in the sera of 74 SSc patients from the years 2000 to 2019 and compared them to IgG4 levels in 80 healthy donors from the Israeli national blood bank. We performed correlation analyses between IgG4 levels and various factors, including age, sex, disease subtype, disease duration, organs involved, and medications taken by the patients.

Results: Our findings revealed significantly lower IgG4 levels in SSc patients compared to healthy participants. SSc patients receiving steroid treatment exhibited prominently lower IgG4 levels. In addition, SSc patients with Raynaud's phenomenon tended to have lower IgG4 levels compared to those without Raynaud's phenomenon.

Conclusions: Our study demonstrates that IgG4 levels are lower in SSc patients. Further research is needed to elucidate whether this observation contributes to the etiology of the disease or if it represents a common manifestation among other autoimmune diseases.

Background: Acute skin infections, like cellulitis or erysipelas, are common and respond well to antibiotic treatment. However, complete resolution of the inflammatory process is often slow and associated with prolonged pain and reduced mobility. Several studies have indicated that acupuncture may effectively treat inflammatory skin diseases.

Objectives: To evaluate the efficacy of acupuncture for treating cellulitis in patients hospitalized in internal medicine departments.

Methods: In this pilot randomized sham-controlled trial, patients hospitalized with cellulitis in internal medicine departments were randomized to acupuncture or sham acupuncture, in addition to standard care. The primary outcome was the degree of improvement in the cellulitis score at day 4 of hospitalization. Secondary endpoints included patient pain self-assessment and local and systemic inflammatory signs.

Results: The study comprised 29 patients; 15 treated with acupuncture, 14 by a sham procedure. At day 4, patients in the acupuncture arm had an improved cellulitis score (4.1 ± 2.8) compared with the sham-control group (7.9 ± 3.3, P = 0.003). Pain intensity based on the Visual Assessment Scale was lower in the acupuncture group 3.8 ± 2.7 vs. 6.3 ± 2.8; P = 0.023. There was no difference in the rate of leukocyte change. However, C-reactive protein significantly decreased to 27.0 ± 22.1 mg/L at day 4 following acupuncture compared to 63.9 ± 51.9 mg/L (P = 0.025).

Conclusions: In our pilot study, we found acupuncture to be efficacious as an adjunctive therapy in the treatment of leg cellulitis. A large-scale trial on the effectiveness of acupuncture for skin infections is needed.

Diabetes mellitus (DM) is a serious and growing global health challenge. The number of people diagnosed with diabetes continues to rise, and it is projected that by 2035 more than 592 million individuals worldwide will have diabetes [1]. DM can impact the heart through various mechanisms. Vascular complications are associated with diabetes and include both epicardial coronary artery and small vessel disease. Cardiomyopathy and heart failure may also occur. Insulin resistance causes cardiomyocytes to have a reduced capacity for glucose utilization, leading to increased uptake of free fatty acids. This, in turn, results in triglyceride storage and lipotoxicity, which contribute to impaired cardiac contractility [2].

Diabetes may lead to the production of advanced glycation end (AGE) products, resulting in an accumulation of reactive oxygen species. This accumulation triggers inflammation that can cause myocyte apoptosis and mitochondrial dysfunction. AGE can also contribute to cardiac fibrosis, which increases myocardial stiffness and results in heart failure with preserved ejection fraction (HFpEF) [2].

Background: Prognostication is complex in patients critically ill with coronavirus disease 2019 (COVID-19).

Objectives: To describe the natural history of ventilated critical COVID-19 patients.

Methods: Due to our legal milieu, active withdrawal of care is not permitted, providing an opportunity to examine the natural history of ventilated critical COVID-19 patients. This retrospective cohort included COVID-19 ICU patients who required mechanical ventilation. Respiratory and laboratory parameters were followed from initiation of mechanical ventilation for 14 days or until extubation, death or tracheostomy.

Results: A total of 112 patients were included in the analysis. Surviving patients were younger than non-survivors (62 years [range 54–69] vs. 66 years [range 62–71], P = 0.01). Survivors had a shorter time to intubation, shorter ventilation duration, and longer hospital stay. Respiratory parameters at intubation were not predictive of mortality. Nevertheless, on ventilation day 10, many of the ventilatory parameters were significantly better in survivors. Regarding laboratory parameters, neutrophil counts were significantly higher in non-survivors on day 1 and C-reactive protein levels were significantly lower in survivors on day 10. Modeling using a generalized estimating equation showed small dynamic differences in ventilatory parameters predictive of survival.

Conclusions: In ventilated COVID-19 patients when there is no active care withdrawal, prognostication may be possible after a week; however, differences between survivors and non-survivors remain small.

Background: One of the major causes of reversible visual impairment is a refractive error, which can be corrected through refractive surgery. Data regarding the outcomes and complications of these procedures exist; however, there is a notable gap in understanding the factors leading to patient rejection, particularly in diverse populations like Israel.

Objectives: To detect clinical risk factors of patients who intend to undergo LASIK procedure and to improve the conversion rates of LASIK procedure in this population.

Methods: The study included a retrospective analysis of patients who were rejected from having refractive surgery in two Enaim Refractive Surgery Centers: Jerusalem and Tel Aviv. Comparisons between centers were conducted using the t-test for continuous variables and Fisher's exact test for categorical data.

Results: Our study included 337 patients who were rejected from having refractive surgery, including 152 (45.1%) who were rejected permanently and 185 (54.9%) rejected temporarily. The most common reasons for permanent rejection were corneal irregularity (n=81, 53.3%), keratoconus (n=27, 17.8%), thin corneas (n=13, 8.6%), and amblyopia (n=10, 6.6%). The most common temporary reasons were unstable refraction (n=96, 51.9%), prolonged use of contact lenses (n=54, 29.2%), and corneal irregularity (n=16, 8.6%).

Conclusions: The leading permanent cause of rejection for refractive surgery was a corneal irregularity, whereas the primary temporary cause was unstable refraction. In a time of rapid technological advancements and growing demand for freedom from glasses, there is an increasing need for more informed and patient-focused refractive correction approaches.

Background: The Agatston coronary artery calcium (CAC) score is a decision-guiding aid for risk assessment and personalized management in the primary prevention of atherosclerotic cardiovascular disease.

Objectives: To explore the real-life clinical experience of CAC testing by characterizing its indications, significance of scores, and corresponding lipid-lowering treatments.

Methods: A retrospective descriptive study of patients treated at the lipids clinic at Rabin Medical Center (Beilinson Campus), who underwent CAC score evaluation between 2017 and 2022 was conducted. The data collected from electronic medical files included demographics, co-morbidities, indications for the test, CAC score levels, and the recommended therapeutic regimen.

Results: The study cohort included 88 patients. The main indication was assessment of the existence of atherosclerosis in cases where there was no clear indication for lipid lowering treatment (65, 74%). In most patients, there was no evidence of atherosclerosis (CAC = 0 AU, n=30) or only mild disease (CAC=1–99 AU, n=35). As the CAC score increased, more patients were prescribed lipid lowering treatments, from very few prescriptions in those with a CAC score of 0 AU and almost 100% among those with score of ≥ 400 AU. The factors that predicted CAC > 0 AU were male sex and older age.

Conclusions: CAC scores should be used more often to determine risk assessment. Further analysis of the implications of scores between 0–400 AU is needed.

Background: Isolated peripheral artery aneurysms are very rare, appearing in fewer than 2% of the general population. The literature reports a few case reports of poliomyelitis patients presenting with unilateral leg paralysis that presented with peripheral aneurysms in the contralateral leg.

Objectives: To compare lower limb arterial diameters in poliomyelitis patients and screen these patients for peripheral aneurysms.

Methods: Poliomyelitis patients older than 55 years of age with unilateral leg paralysis since childhood were prospectively screened by ultrasound duplex during scheduled visits to the outpatient rehabilitation center. These results were compared to the control group. The control groups consisted of healthy adults and patients with childhood poliomyelitis without lower limb paralysis or symmetric bilateral limb paralysis. We measured the diameter of nine arteries in each participant (aorta, bilateral common iliac artery, bilateral common femoral artery, bilateral superficial femoral artery, and bilateral popliteal artery).

Results: The study cohort included 77 participants: 40 poliomyelitis patients with unilateral leg paralysis, 18 poliomyelitis patients with bilateral leg paralysis or without leg paralysis, and 19 non-poliomyelitis patients without leg paralysis. We demonstrated a significant difference between averaged arterial diameters of lower limb arteries in poliomyelitis patients, favoring the strong leg. We were unable to demonstrate an arterial aneurysm in any of the patients.

Conclusions: There is a significant difference between arterial diameters of lower limb arteries in poliomyelitis patients with unilateral leg paralysis in favoring the strong leg.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning.

Objectives: To evaluate our experience with 3D CT cloacagram and assess its results.

Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019–2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome.

Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9–48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication.

Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

Background: Serum ferritin is a sensitive inflammatory biomarker reflecting cell damage and oxidative stress in inflammatory rheumatic diseases. The use of ferritin for assessment of systemic sclerosis (SSc) activity, severity, and prognosis has not been fully elucidated.

Objectives: To assess the correlation between serum ferritin levels and SSc disease parameters, complications, and outcome.

Methods: Demographic, clinical, and laboratory data, including blood levels of ferritin, were collected from files of patients with SSc who were treated at the Rheumatology Institute at Rambam Health Care Campus from January 2004 to July 2021. The study compared SSc patients with elevated levels of ferritin to those with normal levels.

Results: We extracted data of 241 SSc patients (80% female, 60% with diffuse SSc, mean age 54 ± 15.4 years, mean disease duration 6.8 ± 4.5 years). During follow-up, 39% died. Elevated ferritin levels positively correlated with male sex; short disease duration; lung, heart, and kidney involvement; higher modified Rodnan skin score; anemia; elevated levels of creatinine kinase, C-reactive protein, creatinine, and troponin; reduced pulmonary function tests (forced vital capacity and diffusion capacity of the lung for carbon monoxide); and left ventricular ejection fraction. There were no correlations between ferritin levels and pulmonary hypertension or gastrointestinal involvement. Levels of ferritin negatively correlated with anti-centromere antibodies.

Conclusions: In SSc, ferritin can serve as a marker for ongoing systemic inflammation and prognosis, particularly in patients with lung and heart involvement. Further studies on serial ferritin measurement in the management of SSc patients are warranted.

Kidney involvement in systemic sclerosis (SSc) is common with altered kidney function present in approximately half of the patients [1]. Scleroderma renal crisis (SRC), the most severe kidney manifestation, occurs in about 20% of patients with this autoimmune disorder [1]. SRC mainly affects patients with the diffuse cutaneous systemic sclerosis (dcSSc) subtype of the disease, and particularly in those who are seropositive to anti RNA polymerase III antibodies [2]. In recent years, the prevalence of SRC has decreased following the initiation of medication therapy with angiotensin-converting-enzyme inhibitors (ACE-i). Previously, SRC mortality rates were as high as 78%. Contemporary studies in the post-ACE-i era suggest lower rates, with mortality rate ranging from 30% to 36% [3]. Nevertheless, progression to end-stage renal disease (ESRD) is evident and may require renal replacement therapies (RRTs). While renal transplant rates in SSc have increased, they constitute a small proportion of SSc-SRC patients (3–8%) and SSc-ESRD patients (4–17%).