Israel Medical Association Journal

Gaucher disease (GD) is an inherited autosomal recessive genetic disorder caused by mutations in the glucocerebroside (GBA1) gene [1]. These variants result in decreased activity of the lysosomal enzyme β-glucocerebrosidase (GCase), which is essential for breaking down glucocerebroside into glucose and ceramide. Consequently, activated macrophages, known as Gaucher cells, accumulate undegraded glucocerebroside. The phagocytic role and naturally high-level GCase activity of macrophages may partly explain why these cells are particularly affected in GD. The accumulation of glucocerebroside in macrophages causes an expansion in the population of these cells, leading to symptoms like hepatosplenomegaly, thrombocytopenia, anemia, bleeding tendency, growth retardation, and bone issues. Bone marrow infiltration may result in bone infarction, episodes of bone crises, and osteonecrosis, mainly of large joints and less commonly as pathological fractures. These latter skeletal complications are the most critical irreversible consequence of untreated GD, significantly impacting the quality of life of patients, and hence should be avoided by early administration of specific therapy. The accumulation of glucocerebroside in lysosomes has been linked to a pro-inflammatory state [2]. In addition, the misfolding and retention of mutant GCase within the endoplasmic reticulum (ER) has been associated with ER stress and activation of the unfolded protein response, contributing to GD phenotypic heterogeneity, inflammation, and immune dysregulation [3].

The Dina Recanati School of Medicine at Reichman University offers a unique approach to preclinical medical education, combining strong scientific foundations with practical, clinical applications. This 4-year program includes two preclinical years focused on core medical knowledge and two clinical years of rotations. The curriculum emphasizes small-group learning, early clinical exposure, and a system-based block structure. Starting from the first week of the preclinical years, students will participate in biweekly clinical days, using simulations, virtual reality, and patient interactions to develop practical clinical skills. The community clinic mentorship offers real-world experience that complements the clinical program taught in class during the same week. Research is central, with students conducting supervised projects aimed at a medical doctor thesis publication. The teaching model ensures relevance by integrating clinical cases into all courses, guided by practicing physicians. Daily quizzes and block-style assessments replace traditional examination periods, promoting consistent learning. The innovative program balances clinical practice with scientific knowledge, preparing students for the challenges of modern medicine.

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: The impact of the coronavirus disease 2019 (COVID-19) pandemic on patient populations can be divided to direct consequences of the disease and indirect implications of changes imposed on the national healthcare systems. The impact of the later survival of chronic hemodialysis patients is still unknown.

Objectives: To examine the impact of quarantine on health outcomes of dialysis patients.

Methods: In a retrospective case-controlled study, we compared chronic hemodialysis patients from two separate timeframes: during a quarantine period and a parallel time without quarantine.

Results: The study included 344 hemodialysis patients. Baseline characteristics were compared between those enrolled in 2015 and those enrolled in 2020. Despite comparable clinical parameters, a statistically significant increase in the 6-month mortality rate was observed in 2020 (1.2% vs. 6.7%, P = 0.01), primarily attributed to sepsis. Notably, no deaths were attributed to COVID-19 in 2020. Interdialytic weight gain and dialysis quality remained similar between the two groups, with a mild trend toward excessive weight gain in 2020. Secondary outcomes after 6 months did not significantly differ, except for lower sodium values in 2015 compared to 2020.

Conclusions: Dialysis patients experienced disproportionate effects from the COVID-19 pandemic, even with continuous care and no direct virus-related fatalities. The findings showed unintended consequences of quarantine measures, highlighting adverse impact on both physical and mental health. Recognizing and addressing these consequences are imperative for minimizing their impact in future pandemics, emphasizing the importance of proactive measures in healthcare planning.

Nasopharyngeal angiofibromas represent a rare occurrence. They are characterized by vascular fibrous proliferation within the nasopharynx. While histologically benign, they exhibit a local aggressiveness, predominantly afflicting adolescent males. Despite their typically nasopharyngeal location, the exact etiology remains elusive.

Microscopically, angiofibromas manifest as a combination of vascular elements, featuring slit-like capillaries or dilated branched vessels, in addition to a stromal component comprising collagenous matrix and fibroblasts.

To the best of our knowledege, we presented the first documented example of an extra-nasopharyngeal angiofibroma in an adult male, which presented with a distinctive histologic pattern of epithelioid fibrous papule. Clinical manifestations included left-side aural fullness and gradual hearing loss over the course of 5 years. Examination revealed a mass within the left external auditory canal tethered to the posterior wall by a stalk. The audiometric assessment revealed a moderate to severe conductive hearing impairment in the left ear. Surgical excision of the mass was performed, with subsequent histopathological and immunohistochemical analysis unveiling this unforeseen diagnosis.

In this case report, we underscored the potential for angiofibromas to occur in atypical anatomical sites and highlighted the importance of recognizing their benign nature to prevent misdiagnosis as malignant tumors.

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

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: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.

Objectives: To study different triggers for DKA and their effect on outcomes.

Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.

Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35–14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).

Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Background: Intra-articular knee injections (IAKI) are commonly used for diagnostic and therapeutic purposes but may induce anxiety and fear. While existing literature has identified the variance between expected and actual pain levels in various medical procedures, this phenomenon remains unexplored in the context of IAKI.

Objectives: To describe the differences between anticipated and experienced pain recorded during IAKI.

Methods: The study cohort included 50 patients who underwent IAKI by an orthopedic specialist in an outpatient clinic. Patients recruited to the study recorded the anticipated and experienced pain, anxiety index, and factors influencing injection related fear.

Results: The study population (n=50) demonstrated a significant difference between the pain expected before the injection (mean Visual Analogue Scale [VAS] score 6.19) and the actual experienced (mean VAS score 2.07, P-value < 0.001). Significant differences between anticipated and experienced VAS scores were demonstrated for both females and males. There was a significant difference between males and females in terms of estimated VAS score. There was no significant difference between males and females in term of the experienced VAS score. The difference (delta) between expected and experienced pain differed significantly between sexes.

Conclusions: These findings emphasize the importance of educating patients about expected pain levels during IAKI. Presenting this quantified information may reassure patients that the procedure is not as painful as expected, which can potentially increase the compliance.

Background: Although minimally invasive surgery for Crohn’s disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures with an extra-corporeal anastomosis.

Objectives: To evaluate the short- and long-term outcomes of total laparoscopic ileocolic resection with an intracorporeal anastomosis for Crohn’s disease patients.

Methods: We conducted a single-center retrospective review of all patients who underwent primary ileocolic resection for Crohn’s disease between 2010 and 2021. Group A included 34 patients who underwent total laparoscopic ileocolic resection with intracorporeal anastomosis. Group B comprised 144 patients who underwent an open or laparoscopic-assisted procedure.

Results: No differences were noted in operative time (mean 167 minutes vs. 152 minutes, P = 0.122), length of stay (median 6.4 days vs. 7.5 days, P = 0.135), readmission rates (11.8% vs. 13.2%, P = 1), and microscopic involvement of surgical margins (7.7% vs. 18.5%, P = 0.249). Group A had significantly fewer postoperative surgical site infections (2.9% vs. 22.2% respectively, P = 0.013), with no differences in other complications prevalence. After a median follow-up of 46 months, there were similar rates of endoscopic recurrence (47.1% vs. 51.4%, P = 0.72), clinical recurrence (35.3% vs. 47.9%, P = 0.253), and surgical recurrence (2.9% vs. 4.9%, P = 0.722).

Conclusions: Total laparoscopic ileocolic resection with intracorporeal anastomosis for Crohn’s disease is safe and resulted in favorable outcomes in terms of postoperative wound healing. The long-term disease recurrence rates were like those of laparoscopic-assisted and open ileocolic resection.

Echinococcus infections of the liver and lungs are well-known, but cardiac echinococcus is rare, requiring further understanding. A 19-year-old male presented with chest pain, shortness of breath and palpitations. Changes in an electrocardiogram, increased troponin, and a computed tomography (CT) scan revealed a cardiac cyst at the left ventricle’s posterior lateral wall. Medical management included albendazole and praziquantel for 2 weeks followed by surgical cyst removal.

Clinical presentation of cardiac involvement of echinococcus granulosis is variable, requiring high clinical suspicion. Cardiac CT scan and echocardiography provided sufficient information for the diagnosis. The treatment included surgical removal of the cyst and albendazole administration.

Hydatid cyst is a rare zoonotic disease caused by the parasite Echinococcus granulosus [1]. The incidence in endemic areas is about 1–200 cases per 100,000 in population [2].

The liver (60–70% of cases) and lungs (20–30%) are the most common locations of hydatid cysts, with rare cardiac involvement of only 0.05% to 2% of all cases [3], with the left ventricle most frequently involved (60%) [2,4].

Background: Pediatric urolithiasis is relatively uncommon and is generally associated with predisposing anatomic or metabolic abnormalities. In the adult population, emergency department (ED) admissions have been associated with an increase in ambient temperature. The same association has not been evaluated in the pediatric population.

Objectives: To analyze trends in ED admissions due to renal colic in a pediatric population (≤ 18 years old) and to assess the possible effect of climate on ED admissions.

Methods: We conducted a retrospective, multicenter cohort study, based on a computerized database of all ED visits due to renal colic in pediatric patients. The study cohort presented with urolithiasis on imaging during their ED admission. Exact climate data was acquired through the Israeli Meteorological Service (IMS).

Results: Between January 2010 and December 2020, 609 patients, ≤ 18 years, were admitted to EDs in five medical centers with renal colic: 318 males (52%), 291 females (48%). The median age was 17 years (IQR 9–16). ED visits oscillated through the years, peaking in 2012 and 2018. A 6% downward trend in ED admissions was noted between 2010 and 2020. The number of ED admissions in the different seasons was 179 in autumn (30%), 134 in winter (22%), 152 in spring (25%), and 144 in summer (23%) (P = 0.8). Logistic regression multivariable analysis associated with ED visits did not find any correlation between climate parameters and ED admissions due to renal colic in the pediatric population.

Conclusions: ED admissions oscillated during the period investigated and had a downward trend. Unlike in the adult population, rates of renal colic ED admissions in the pediatric population were not affected by seasonal changes or rise in maximum ambient temperature.

Background: Completing internal medicine specialty training in Israel involves passing the Israel National Internal Medicine Exam (Shlav Aleph), a challenging multiple-choice test. multiple-choice test. Chat generative pre-trained transformer (ChatGPT) 3.5, a language model, is increasingly used for exam preparation.

Objectives: To assess the ability of ChatGPT 3.5 to pass the Israel National Internal Medicine Exam in Hebrew.

Methods: Using the 2023 Shlav Aleph exam questions, ChatGPT received prompts in Hebrew. Textual questions were analyzed after the appeal, comparing its answers to the official key.

Results: ChatGPT 3.5 correctly answered 36.6% of the 133 analyzed questions, with consistent performance across topics, except for challenges in nephrology and biostatistics.

Conclusions: While ChatGPT 3.5 has excelled in English medical exams, its performance in the Hebrew Shlav Aleph was suboptimal. Factors include limited training data in Hebrew, translation complexities, and unique language structures. Further investigation is essential for its effective adaptation to Hebrew medical exam preparation.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.