Israel Medical Association Journal

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.

Background: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost.

Objectives: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019.

Methods: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference.

Results: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019.

Conclusions: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.

Late arrival ST-segment elevation myocardial infarction (STEMI) is defined as a patient-related delay > 12 hours. It is estimated to represent a significant portion of STEMI patients. As reflected by society guidelines, this group of patients impose great therapeutic challenge, namely due to controversy in the literature regarding optimal care, together with major adverse clinical outcomes [1]. In addition to a possible myocardial infarction (MI), mechanical complications include ventricular septal defect (VSD), left ventricular (LV) free wall, or papillary muscle rupture. Prompt diagnosis and intervention are crucial to improve outcomes as post-infarction ventricular septal defect (PIVSD) carries a high mortality rate. We describe the successful management of a large VSD complicated by cardiogenic shock in a latecomer STEMI patient with complex coronary artery disease (CAD).

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied.

Objectives: To investigate the demographic and clinical profile of HS in the Israeli Arab population.

Methods: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups.

Results: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, p < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, p < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, p = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, p = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs.

Conclusions: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Background: Condylar hyperplasia is a non-neoplastic overgrowth of the mandibular condyle. The disorder is progressive and causes gradual jaw deviation, facial asymmetry, and dental malocclusion. The only treatment capable of stopping hyperplastic growth is surgical condylectomy to remove the upper portion of the condyle containing the deranged growth center. When this procedure is conducted in proportion to the length of the healthy side it may also correct the jaw deviation and facial asymmetry.

Objectives: To assess the degree to which condylectomy corrects the asymmetry and to determine the proportion of patients after condylectomy who were satisfied with the esthetic result and did not desire further corrective surgery.

Methods: We conducted a retrospective analysis of medical records of patients who underwent condylectomy that was not followed by corrective orthognathic surgery for at least 1 year to determine the degree of correction of chin deviation and lip cant. Patient satisfaction from treatment or desire and undergo further corrective surgery was reported.

Results: Chin deviation decreased after condylectomy from a mean of 4.8⁰ to a mean of 1.8⁰ (P < 0.001). Lip cant decreased after condylectomy from a mean of 3.5⁰ to a mean of 1.5⁰ (P < 0.001). Most patients (72%) were satisfied with the results and did not consider further corrective orthognathic surgery.

Conclusions: Proportional condylectomy could be a viable treatment to both arrest the condylar overgrowth and achieve some correction of the facial asymmetry.

Background: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. 

Objectives: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children.

Methods: We assessed 54 children aged 2–17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification.

Results: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36).

Conclusions: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

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].

Inflammatory myopathies include polymyositis, necrotizing autoimmune myositis, dermatomyositis, juvenile inflammatory myopathy, and inclusion body myositis. These diseases are classified based on the different clinical and pathological characteristics unique to each of them [1]. Dermatomyositis is a rare disease with an incidence of 6–10 cases/1,000,000 a year with the highest incidence in the 7th decade of life as reported by a Norwegian cohort in a Caucasian population [2].

Diagnosis of dermatomyositis is based on typical signs and symptoms combined with laboratory results, imaging, and electromyography findings and muscle biopsy. Historically, the diagnosis of dermatomyositis was based on the classification criteria named after Bohan and Peter published in 1975. Many other classification criteria were proposed subsequently, the latter by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR), which were published in 2020 [3].

The clinical features of dermatomyositis are diverse. Skin manifestations can accompany or precede muscle weakness. Classical skin findings include periorbital heliotrope rash and a rash of the upper chest, back, and shoulders, known as the V sign and shawl sign respectively, as well as the Gottron's papules on the knuckles. Another skin appearance is subcutaneous calcifications that break periodically through the skin causing ulcerations. Dermatomyositis usually manifests as a symmetrical proximal muscle weakness but can present with preserved strength called amyopathic dermatomyositis [1].

Background: On 7 April 1933, the Nazi Law for the Restoration of the Professional Civil Service was enacted. The law triggered the dismissal of most Jewish medical staff from German universities. A few Jewish professors in Berlin were permitted to continue their academic activity with restrictions. Those professors were gradually dismissed as laws and restrictions were enforced.

Objectives: To identify the last Jewish medical professors who, despite severe restrictions, continued their academic duties and prepared students for their examinations in Berlin after the summer of 1933.

Methods: We reviewed dissertations written by the medical faculty of Berlin from 1933 to 1937 and identified Jewish professors who mentored students during those years.

Results: Thirteen Jewish tutors instructed dissertations for the medical examinations after the Nazi regime seized power. They were employees of different university hospitals, including the Jewish hospitals. We did not identify Aryan students instructed by Jewish professors. The professors were active in different medical disciplines. Half of the reviewed dissertations were in the disciplines of surgery and gynecology. The last Jewish tutors were dismissed in October 1935. However, some of their studies were submitted for examination after that date.

Conclusions: After the Nazi regime seized power, academic activities and medical research by Jewish professors declined but did not stop. However, these professors worked with only Jewish students on their theses. Most dissertations were approved and examined after the Jewish academics were dismissed by the university, in some cases even after they left Germany.

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Background: The prevalence of Group A streptococcus (GAS) carriage among adults is studied less than in children. The variability of reported carriage rates is considerably large and differs among diverse geographic areas and populations.

Objectives: To evaluate the prevalence of GAS carriage among adults in Israel.

Methods: In this prospective study, conducted in a large healthcare maintenance organization in Israel, we obtained pharyngeal cultures from adults attending the clinic without upper respiratory tract complaints or fever. Patient data included sex, age, number of children, and religious sectors.

Results: From May to December 2022, eight family physicians collected a total of 172 throat swabs (86% response rate). The median age was 37 years (range 18–65); 72.7% were females, 22.7% were ultra-Orthodox Jewish, and 69.2% had children. The prevalence of GAS carriage was 6.98%, 95% confidence interval (95%CI) 3.7%–11.9%. GAS carriers were younger (31.7 vs. 39.3 years, P = 0.046), and the majority were ultra-Orthodox Jews (58.3% vs. 20%, P = 0.006). All GAS carriers were from lower socioeconomic status. When assessing risk factors for GAS carriage using multivariate analysis, only being an ultra-Orthodox Jew was positively related to GAS carriage (adjusted odds ratio 5.6, 95%CI 1.67–18.8).

Conclusion: Being an ultra-Orthodox Jew was the single variable associated with a GAS carriage, which may be related to having many children at home and living in overcrowded areas. Primary care physicians in Israel should recognize this situation when examining patients with sore throats, mainly ultra-Orthodox Jews.

Inappropriate implantable cardiac defibrillator (ICD) shock due to electromagnetic interference (EMI) induced by electrocautery is a well-known theoretical association but is rarely reported [1]. We report a case of EMI induced by electrocautery causing inappropriate ICD shock, underlining that, with the use of monopolar cautery, not only the location of the surgery but also electrodispersive pad (EDP) placement may be important to avoid EMI.

Neuroendocrine tumors (NETs) are a group of rare, heterogenous neoplasms that maintain unique morphologic and clinical features of neuroendocrine neoplasia and account for approximately 0.5% of all newly diagnosed malignancies. NETs are divided into two groups based on their histopathological morphology: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Well differentiated NETs are classified as G1, G2, or G3 based on their proliferation rate, whereas NECs are highly proliferative and poorly differentiated by definition [1]. Neuroendocrine neoplasms can occur almost anywhere in the body; however, they are most often seen in the gastrointestinal tract, pancreas, and lungs [2]. The extrahepatic bile duct is one of the rarest primary sites for NETs, accounting for 0.1% to 0.2% of NETs of the gastrointestinal tract [3]. Signet ring cell bile duct NETs are extremely uncommon and have no established incidence and prognosis due to their rarity. There is sparse information available regarding these tumors, and only a few cases have been reported in the literature to date. In this report, we presented the clinical course and surgical management of a 31-year-old female patient with a Klatskin signet ring cell NET.

Testimonies, articles, or books on Nazi medical atrocities written by physicians, whether Holocaust survivors or not and whether written during the Holocaust or just after 1945, are very important teaching materials. The professional views of physicians give special insight. In this review we highlighted a few biographical and eyewitness accounts by Jewish physicians about their medical activities and the inhuman medical activities of the Nazis. The activities of Jewish doctors in the ghettos and camps, including research projects on hunger or infectious diseases, are truly suitable case studies. We presented representative case studies that can be effectively introduced in medical school curricula.