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.

Background: Giant cell arteritis (GCA) is a large vessel vasculitis predominantly affecting patients over 50 years, typically managed with glucocorticoids, with treatment varying on individual patient needs. While effective for GCA, long-term glucocorticoids use poses significant risks, including the development of osteoporosis, a metabolic bone disease common in older individuals. This overlap poses a significant clinical challenge, as the treatment for GCA inadvertently raises the risk of osteoporosis and necessitates careful balance to manage both conditions effectively.

Objectives: To investigate the occurrence of osteoporosis and other co-morbid conditions in patients with GCA treated with glucocorticoids.

Methods: A retrospective cross-sectional analysis of GCA patients examined the correlation between GCA and osteoporosis by searching the Clalit Health Service database for patients over 50 years of age from January 2002 to January 2018. In addition, we conducted a logistic regression analysis stratifying for other co-morbidities to evaluate the independent association between GCA and osteoporosis.

Results: In total, 6607 GCA patients were compared with 36,066 age- and sex-matched controls. The study revealed a higher prevalence of osteoporosis in the GCA group (43%) compared to controls (27%) (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.95–2.17). In addition, hypertension, hyperlipidemia, diabetes mellitus, and ischemic heart disease were more prevalent among GCA patients. After stratifying for cardiovascular co-morbidities, GCA remained independently associated with osteoporosis (OR 2.1, 95%CI 1.96–2.26, P < 0.001).

Conclusions: Glucocorticoid-treated GCA is independently associated with osteoporosis. Healthcare providers must consider this added aspect of GCA for the treatment and management of patients.

A 38-year-old immunocompetent male with a history of Hodgkin's lymphoma in remission presented to the emergency department at Rambam Hospital with infectious mononucleosis due to an acute cytomegalovirus (CMV) infection. He was also diagnosed with portal vein thrombosis (PVT). After a thorough laboratory and radiological investigation, these two diagnoses were found to be related. No other explanation was identified except for transiently detected antiphospholipid antibodies, which were assumed to be provoked by the CMV infection. In this review, we investigated the relationship between CMV infection and a hypercoagulable state. We searched the PubMed database for case reports, clinical reviews, and meta-analyses that reviewed the relationship between CMV infection and deep vein thrombosis. The incidence of thromboembolism in patients with acute CMV infection was reported to be as high as 6.4%. In addition, anti-cardiolipin antibodies were more commonly present at the time of PVT diagnosis among CMV-positive patients compared to CMV-negative patients, although these antibodies disappeared in most cases. To the best of our knowledge, there is no evidence of added benefit from antiviral therapy in patients with CMV-associated thrombosis. CMV infection may serve as a trigger for a transient hypercoagulable state.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure (HF) secondary to left ventricular systolic dysfunction (defined as left ventricular ejection fraction [LVEF]) < 45% toward the end of pregnancy or in the months following delivery, where no other cause of HF is found. Complete understanding of the etiology is lacking, with higher incidence seen in advanced maternal age, multiple gestations, preeclampsia, and anemia [1]. Potential suggested causes include pathological immune response, hormonal abnormalities, stress cytokines, and nutritional deficiencies. Genetic predisposition was demonstrated in some PPCM, most commonly pathogenic loss-of-function truncating variants in Titin gene (TTN) [1]. Other causative genes reported are DMD, LAMP2, DSP, MYH6, SYNM, TPM1, and VCL [1].

Esophageal lung is a rare congenital malformation. We present a case of a full-term infant with an esophageal lung presenting as a white lung combined with VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) and dysmorphic features. A right pneumonectomy was successfully performed.

Leeches belong to the class Hirudinea of the phylum Annelida. There are approximately 650 known species of leeches, some terrestrial, some marine, and most freshwater. Although some are predators, most leeches are hematophagous, and all are hermaphrodites [1].

The leeches Limnatis nilotica, Praeodella guineensis, Myxobdella africana, Dinobdella ferox, and Hirudo troctina occasionally invade human orifices such as the eyes, nasopharyngeal region, urethra, vagina, and rectum. They cause mucosal, orificial, vesical, or internal hirudiniasis depending on the location of the leech [1]. Infection usually occurs by drinking contaminated water or bathing in stagnant streams, pools, or springs. While most blood-feeding leeches feed as ectoparasites for short periods of time, those that feed on mucous membranes have been known to remain in an orifice for days or weeks. Hematuria, hemoptysis, hematemesis, epistaxis and rectal bleeding, dysphonia, cough, tickling, and dyspnea may occur [1].

We report the case of a male patient who entered freshwater pools in Israel and was infected with L. nilotica.

Liver transplantation (LT) remains the only definitive treatment for most types of liver failure. However, it is considered a highly technically complex surgery performed in a critically ill patient population and is, hence, associated with significant morbidity and mortality. Peroneal neuropathy with foot drop has been intermittently reported as a complication following LT, with an incidence ranging from 1.4% to 13.3% [1-4]. This debilitating condition is characterized by an inability to lift the forefoot due to paralysis or significant weakness of the dorsiflexor muscles. While it may not appear to be a serious complication, it can significantly impair gait, increase the risk of falls, and ultimately affect ambulation and the ability to perform daily activities [5].

In this case communication, we described two cases of foot drop following LT at Rabin Medical Center (Beilinson Campus), Petah Tikva, Israel. Our research joins a growing body of evidence and raises awareness about foot drop as an underreported yet debilitating complication. It underscores the importance of increased vigilance and describes our preventive measures adopted to reduce future incidents.

Background: Allergic rhinitis (AR) is a common illness. Worldwide prevalence varies between 5% and 50% depending on self-reported surveys, test-based studies, geographic location, and age. Despite the clinical relevance of AR in the Israeli population, few studies have characterized the sensitization profiles and key pollen aeroallergen.

Objectives: To describe the most common aeroallergens eliciting a positive skin prick test (SPT) in AR patients across three different main climate zones in Israel.

Methods: We evaluated SPT of aeroallergen sensitization in 1308 AR patients from three topographically and climatically different areas of Israel, describing humidity levels, temperature, and urbanization.

Results: The overall prevalence of positive SPT among patients presenting with AR symptoms was 86%. Indoor aeroallergen sensitization was observed in 76% of patients. Monosensitization was noted in 20% of patients, and polysensitization was noted in 65%. Among the 1308 cases of AR, the top four aeroallergens were mites, olive tree pollen, grass pollen, and cat dander. The top aeroallergen in Israel's central district were mites (62%), olive tree pollen (36%), and grass pollen (30%). In the coastal plains, mites (92%), cat dander (36%), and olive tree pollen (33%) were most prevalent, and in the south mites (77%), olive tree pollen (30%), and grass pollens (26%) were most common.

Conclusions: The top four aeroallergens eliciting a positive SPT were mites, olive tree pollen, grass pollen, and cat dander. Identification of a major aeroallergen can tailor the allergist's SPT panels and specify which aeroallergen should be used for immunotherapy.

Background: Cardiac implantable electronic devices (CIEDs) with endocardial leads crossing the tricuspid valve can lead to or worsen tricuspid regurgitation (TR), causing substantial morbidity and mortality. Despite a recent randomized controlled study revealing a low short-term incidence of device-related TR (DRT) post-CIED implantation, uncertainties persist regarding the efficacy of intra-procedural 2-dimensional transthoracic echocardiography (2DTTE) in preventing long-term TR.

Objectives: To conduct a long-term follow-up study on patients with CIED implants based on a previous study conducted at our hospital.

Methods: In a retrospective study at Assuta Ashdod Medical Center (2018–2019), patients undergoing de-novo CIED implantation with (n=39, group 1) or without (n=51, group 2) intra-procedural 2DTTE were analyzed. Clinical, demographic, and long-term (> 1 year) echocardiographic data were collected and compared.

Results: The study included 90 patients (mean age 72.3 ± 11.0 years, 63% male, 23% ICD, 50% active leads, follow-up 32.8 ± 11 months). TR aggravation was found in 25% of patients (13 in group 1, 10 in group 2), with no statistical difference between groups. Multivariate analysis identified a history of atrial fibrillation (AF) as the sole significant factor in long-term TR deterioration (OR=3.44, 95%CI 1.13–10.43, P = 0.029). Other clinical, demographic, echocardiographic, and device-related factors did not significantly contribute to long-term DRT.

Conclusions: After one-year post-CIED implantation, the incidence of DRT significantly increases. Intra-procedural 2DTTE does not effectively reduce long-term DRT, suggesting that implantation-related mechanisms are less likely the primary cause. AF likely plays a major role in the pathogenesis of long-term TR in this subset post-CIED implantation.

Background: Cardiac implantable electronic devices (CIEDs) are associated with risks of device-related infections (DRI) impacting major adverse outcomes. Staphylococcus aureus (SA) is a leading cause of early pocket infection and bacteremia. While studies in other surgical contexts have suggested that nasal mupirocin treatment and chlorhexidine skin washing may reduce colonization and infection risk, limited data exist for CIED interventions.

Objectives: To assess the impact of SA decolonization on DRI rates.

Methods: We conducted a retrospective, single-center observational study on consecutive patients undergoing CIED interventions (March 2020–March 2022). All patients received pre-procedure antibiotics and chlorhexidine skin washing. Starting in March 2021, additional pre-treatment with mupirocin for SA decolonization was administered. DRI rates within 6 months post-implantation were compared between patients treated according to guidelines (Group 1) and those receiving mupirocin in addition to the recommended guidelines (Group 2).

Results: The study comprised 276 patients (age 77 ± 10 years; 60% male). DRI occurred in five patients (1.8%);80% underwent cardiac resynchronization therapy procedures. In Group 1 (n=177), four patients (2.2%) experienced DRI 11–48 days post-procedure; three with pocket infection (two with negative cultures and one with local Pseudomonas) and one with methicillin-sensitive SA endocarditis necessitating device extraction. In Group 2 (n=99), only one patient (1%) had DRI (Strep. dysgalactiae endocarditis) 135 days post-procedure (P = NS).

Conclusions: The routine decolonization of SA with mupirocin, in addition to guideline-directed protocols, did not significantly affect DRI rates. Larger prospective studies are needed to evaluate the preventive role of routine SA decolonization in CIED procedures.

Background: Diabetic ketoacidosis (DKA) poses a significant medical emergency in both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients. Recent attention has focused on the emergence of euglycemic DKA associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Objectives: To understand the epidemiology and outcomes of DKA, particularly in T2DM patients.

Methods: We conducted a retrospective cohort analysis of 204 patients admitted with DKA to Shamir Medical Center (2013–2021). We assessed demographics, clinical characteristics, and outcomes. Patients were stratified by diabetes type and SGLT2 inhibitor treatment status.

Results: Among the 204 patients with DKA, 38.2% had T2DM. Patients with T2DM exhibited older age, higher co-morbidity burden, and greater prevalence of microvascular complications compared to T1DM patients. Mortality rates were notably higher among T2DM patients, despite similar DKA severity at presentation, including in-hospital mortality rates of 6.4% vs. 0%, P < 0.05, and 90-day mortality rates of 7.7% vs. 0%, P < 0.05. T2DM was independently associated with adverse hospitalization outcomes, including a composite of rehospitalization, prolonged hospital stays, and mortality (odds ratio 2.68, 95% confidence interval 1.302–5.557). SGLT2 inhibitor treatment did not affect hospitalization outcomes of patients with T2DM.

Conclusions: Our findings underscore the importance of recognizing DKA as a substantial complication in diabetic patients, particularly those with T2DM. Vigilance in management, adherence to DKA guidelines, and awareness of triggers such as SGLT2 inhibitors are crucial for improving outcomes in this population.

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.

In this case report, we elucidated the complex etiology of new-onset ascites through the unusual presentation of a 32-year-old female with abdominal swelling, oliguria, and acute renal failure. This patient's ascites was attributed to urinary bladder rupture, a rare but critical consideration in differential diagnoses. Highlighting the significance of this case, bladder rupture without recent trauma history, especially post-gynecological surgery, poses a diagnostic challenge due to its rarity and potential for severe morbidity and mortality if not promptly recognized and managed. Our patient's journey, from initial symptoms to the eventual discovery of bladder rupture, underscores the necessity of considering this diagnosis in similar clinical scenarios. The case uniquely demonstrates pseudo-renal failure, a phenomenon resulting from reversed dialysis across the peritoneal membrane, which further complicated the diagnostic process.

Background: On 7 October 2023, Hamas lunched a massive terror attack against Israel. The first weeks after were characterized with great uncertainty, insecurity, and fear.

Objectives: To evaluate the effect of the first 2 months of the Iron Swords war on obstetrical emergency attendance and the corresponding perinatal outcomes.

Methods: We conducted a single center retrospective cohort study of all singleton births between 7 October and 7 December 2023. Prenatal emergency labor ward admission numbers and obstetric outcomes during the first 2 months of the war were compared to the combined corresponding periods for the years 2018–2022.

Results: During the initial 2 months of the conflict 1379 births were documented. The control group consisted of 7304 deliveries between 2018 and 2022. There was a decrease in daily emergency admissions to the labor ward during the first 5 weeks of the conflict compared to the corresponding periods in the preceding years (51.8 ± 15.0 vs. 57.0 ± 13.0, P = 0.0458). A notable increase in stillbirth rates was observed in the study group compared to the control group (5/1379 [0.36%] vs. 7/7304 [0.1%]; P = 0.014). Both groups exhibited similar gestational ages at birth, rates of preterm and post-term delivery, neonatal birthweights, mode of delivery, and induction of labor rates.

Conclusions: In the initial weeks following Hamas's attack on Israel, there was a notable decrease in admissions to the prenatal emergency labor ward. This decline coincided with an increase in the rate of stillbirths among a population not directly involved in the conflict.

Background: Fetal weight estimation at term is a challenging clinical task.

Objectives: To evaluate the association between peripheral white blood cell (WBC) count of the laboring women and neonatal birth weight (BW) for term uncomplicated pregnancies.

Methods: We conducted a single-center, retrospective cohort study (2006–2021) of women admitted in the first stage of labor or planned cesarean delivery. Complete blood counts were collected at admission. BW groups were categorized by weight (grams): < 2500 (group A), 2500–3499 (group B), 3500–4000 (group C), and > 4000 (group D). Two study periods were used to evaluate the association between WBC count and neonatal BW.

Results: There were a total of 98,632 deliveries. The dataset analyses showed a lower WBC count that was significantly and linearly associated with a higher BW; P for trend < 0.001 for women in labor. The most significant association was noted for the > 4000-gram newborns; adjusted odds ratio 0.97, 95% confidence interval 0.96–0.98; P < 0.001; adjusted for hemoglobin level, gestational age, and fetal sex. The 2018–2021 dataset analyses revealed WBC as an independent predictor of macrosomia with a significant incremental predictive value (P < 0.0001). The negative predictive value of the WBC count for macrosomia was significantly high, 93.85% for a threshold of WBC < 10.25 × 10³/µl.

Conclusions: WBC count should be considered to support the in-labor fetal weight estimation, especially valuable for the macrosomic fetus.