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 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.

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.

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: The coronavirus disease 2019 (COVID-19) pandemic posed significant challenges to healthcare systems worldwide, including a surge in the use of extracorporeal membrane oxygenation (ECMO).

Objectives: To compare outcomes and costs of COVID-19 and non-COVID-19 adult patients treated with ECMO in the intensive care unit (ICU) at Tel Aviv Sourasky Medical Center.

Methods: We conducted a retrospective study. Clinical outcomes, ECMO duration, ICU and hospital length of stay (LOS), and healthcare costs were examined and compared between the two groups.

Results: A total of 119 patients were treated with ECMO between 2016 and 2023; 56 (47.1%) diagnosed with COVID-19. The study found no significant difference in mortality rates between COVID-19 and non-COVID-19 patients. However, COVID-19 patients experienced significantly longer ECMO durations and ICU LOS. Hospitalization and ECMO operation costs were notably higher for COVID-19 patients, but overall admission costs were lower compared to non-COVID-19 patients, with cost of surgical interventions, consultations and imaging contributing to the price gap.

Conclusions: Despite longer durations of ECMO and LOS, the economic burden of ECMO in COVID-19 patients was significantly lower than non-COVID-19 patients. Strict patient selection should be utilized, a fortiori during times of surge-capacity.

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: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation.

Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles.

Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay.

Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015).

Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

Background: Hemodialysis requires reliable, recurrent access to the circulatory system. Central venous tunneled dialysis catheters (TDC) are frequently used for patients receiving hemodialysis as a bridge to permanent vascular access or as a final option. TDC are prone to complications such as infection and dysfunction.

Objective: To assess the prevalence and predictors of TDC dysfunction in a cohort of chronic hemodialysis patients.

Methods: This single-center, retrospective study was based on data from an electronic database of chronic hemodialysis patients during 5 years of follow-up.

Results: A total of 625 TDC were inserted in 361 patients, of which 234 (37.4%) were replaced due to dysfunction. The main insertion site was the right internal jugular vein. Diabetes mellitus was an important predictor of TDC dysfunction and was significantly correlated with TDC extraction. Chronic anticoagulation and antiplatelet treatment did not affect the rate of TDC dysfunction or replacement.

Conclusions: TDC use for chronic dialysis patients is increasing and dysfunction is a major problem. In our study, we highlighted the high prevalence of TDC dysfunction and the need for further research to improve hemodialysis access as well as TDC patency and function.

The use of smaller-diameter, pencil-point spinal needles has increased to reduce post-dural puncture headaches in obstetric patients. However, this therapy has also led to more needle deformation and breakage. While risk factors and prevention are described, there is limited literature on management when breakage occurs.

The utilization of neuraxial techniques for labor analgesia and cesarean delivery has experienced a consistent increase in recent years [1]. Spinal anesthesia has emerged as the preferred technique for cesarean deliveries due to its advantages, including a reduction in morbidity and mortality, decreased complications related to airway management, reduced bleeding, improved bonding with the baby, and better outcomes for newborns [2]. While the adoption of smaller diameter, non-cutting bevel spinal needles has successfully reduced the incidence of post-dural puncture headaches in obstetric patients, it has also given rise to complications such as spinal needle deformation and breakage [3,4]. The current understanding of the incidence of neuraxial needle breakage remains limited, with estimated incidences reported between approximately 1 in 5,000 to 1 in 11,000 spinal anesthesia procedures performed [4]. Although numerous case reports have documented broken needles during attempted neuraxial anesthesia, the existing literature predominantly focuses on associated risk factors and preventive measures for this complication [3]. However, there is a lack of literature regarding the subsequent management once this adverse event has transpired. In this report, we present a case involving a broken spinal needle during an attempt to perform spinal anesthesia for an urgent cesarean delivery. By sharing this case, we shed light on the management strategies and considerations following such an event.

Hepatitis E Virus (HEV), a single-stranded RNA virus, is the leading cause of viral-induced acute liver failure globally. It is estimated to infect 20 million people annually, resulting in 3.3 million symptomatic cases and 44,000 deaths, worldwide [1]. Transmission is fecal-oral through contaminated food and water, zoonotic spread, or blood transfusions, and usually results in a self-limiting disease. While prevalent in resource-limited countries, cases are sporadic in the developed world [1]. Established risk factors for severe HEV infection include pregnancy, immunocompromised state, and underlying liver disease, while reports of malignancy as a predisposing factor are not well documented [1]. Here we present a case of a patient who, without established risk factors, developed a severe HEV infection leading to multiorgan failure and death.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated condition characterized by fibro-inflammatory lesions with lymphoplasmacytic infiltration. Diagnosis traditionally relies on histopathological findings, including the presence of IgG4+ plasma cells. However, due to challenges in biopsy accessibility, additional measures are needed to facilitate diagnosis.

Objectives: To identify additional parameters for characterizing IgG4-RD patients.

Methods: We compared several circulating factors between a cohort of patients with IgG4-RD disease seen at our hospital between 2017 and 2023 and healthy controls.

Results: Among 16 suspected patients, 13 were confirmed to have IgG4-RD, and 3 were classified as highly likely. Comparison with controls revealed differences in white blood cell count (WBC) (Folf change (FC) 1.46, P < 0.05), plasmablasts (FC 3.76, P< 0.05), plasmablasts CD38 (FC 1.43, P < 0.05), and CD27 (FC 0.66, P = 0.054), thus highlighting potential markers for IgG4-RD diagnosis. Treatments with steroids/rituximab tend to reduce plasmablast (FC 0.6) and IgG4 (FC 0.28) levels and to increase Gal-3 levels.

Conclusions: Levels of plasmablasts are a significant diagnostic feature in IgG4-RD. Healthy individuals have a lower level of plasmablasts. Elevated Gal-3 in serum of patients with IgG4-RD suggests a role in plasmablast activation. CD38/CD27 expression by plasmablasts emerges as a potential marker. Further research on a larger cohort is needed to confirm these findings.

Background: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications.

Objectives: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM.

Methods: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared.

Results: The cohort included 89 women: 49 with HbA1c 6–8%, 29 with HbA1c 8–10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes.

Conclusions: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Artificial intelligence in ophthalmology is used for automatic diagnosis, data analysis, and predicting responses to possible treatments. The potential challenges in the application and assimilation of artificial intelligence include technical challenges of the algorithms, the ability to explain the algorithm, and the ability to diagnose and manage the medical course of patients. Despite these challenges, artificial intelligence is expected to revolutionize the way ophthalmology will be practiced. In this review, we compiled recent reports on the use and application of deep learning in various fields of ophthalmology, potential challenges in clinical deployment, and future directions.

Background: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective.

Objectives: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses.

Methods: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose.

Results: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (21² vs. 31⁵ weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048–0.926, P = 0.039).

Conclusions: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

The cause of death for Pharaoh Tutankhamun (ca. 1330–1324 BCE) is still unknown despite the advancement in modern paleopathology and the introduction of computed tomography mummy examination and modern molecular pathology, including PCR-based gene analysis. Many speculations regarding his unexpected death have been published, including crush injury, infectious diseases such as malaria, and hereditary disease. We discuss for the first time all these events that could have ultimately caused Tutankhamun's sudden death, particularly sickle cell disease, which can cause osteonecrosis and lead to walking disability, bone deformities, and fragility. Malaria-associated tropical splenomegaly, as an acquired infectious disease, and the crush injury, which represents an acute event, were verified by a left distal femur fracture that contributed to splenic rupture as a major fatal event. We highlight important issues that can provide clinicians and clinical care practitioners with a broad vision while analyzing such cases.