Israel Medical Association Journal

The Holocaust represents an extreme failure of medical ethics, with physicians actively involved in crimes against humanity. Rheumatology is directly affected through eponyms that honor Nazi perpetrators and through persistent musculoskeletal consequences observed in Holocaust survivors. In this article, we critically analyzed symbolic (nomenclature) and biological (trauma-related disability) legacies of Nazism in rheumatology. Narrative reviews of PubMed/MEDLINE, Scopus, and Israel Medical Association Journal (IMAJ) as well as key historiographic analyses and clinical studies of musculoskeletal outcomes among Holocaust survivors were included. Ethical codes emerging post-Holocaust (Nuremberg Code and Declaration of Helsinki) were integrated. Renaming Reiter’s syndrome as reactive arthritis and Wegener’s granulomatosis as granulomatosis with polyangiitis represents ethical correction. Clinical evidence shows Holocaust survivors experience such as reduced functional recovery after hip fracture, lower perceived health despite similar objective measures, and greater cardiovascular burden impairing rehabilitation tolerance. Rheumatology must align nomenclature with ethical responsibility and recognize trauma-associated musculoskeletal vulnerability. Historical memory should guide clinical decisions, language, and education

It is 3:00 in the morning at an Israeli medical center. The rhythmic beeping of monitors pierces the silence as an on-call team gathers around a patient's bed. The team includes a Jewish doctor, a Muslim nurse, and a Christian physician. In these critical moments, the only language spoken is the language of medicine–a seamless blend of physiology, pharmacology, and an ancient medical oath.

For us in Israel, this reality is natural and common. Yet, viewed through a historical lens, particularly against the backdrop of World War II when medicine itself was weaponized and conscripted into an extermination machine, this collaboration was nothing short of a monumental triumph of the human spirit. In this editorial, I invite you on a historical journey to revisit two profound narratives where physicians from diverse backgrounds transformed their clinical knowledge and authority into instruments of life and resistance.

In this study on Holocaust (Shoah) survivors, we reviewed accumulated data demonstrating an increased incidence of diabetes and cancer in the later years of survivors. We evaluated the status of high nutrition, compared to the low incidence of the same morbidities affecting the prisoners in the ghettos of World War II, while experiencing severe nutritional deficiency. The assumption of the high glucose requirement of cancer cells is discussed.

Phlycten syndrome was described as a traumatic surgical syndrome of the lower limbs, beginning as streptococcal cellulitis and progressing to necrotizing edema in individuals with starvation-induced hypoalbuminemia and electrolyte imbalance. Independently documented by three physicians during their imprisonment in Nazi concentration camps in World War II, the syndrome also developed when edematous, emaciated prisoners were flogged, causing rapid progression to gangrene and sepsis.

A 55-year-old male with a history of Dubin-Johnson syndrome (DJS), obesity, and smoking presented to the emergency department with generalized weakness and jaundice. On admission, he was hypotensive (blood pressure 87/56 mmHg), and profound jaundice was noted. Laboratory investigations revealed severe acute kidney injury with a creatinine level of 5.53 mg/dl and blood urea nitrogen of 92 mg/dl. Liver function tests were mildly elevated, and his lipid profile was within normal limits. Total bilirubin was markedly elevated at 52.5 mg/dl, predominantly direct (40.9 mg/dl). The patient was anuric at the time of catheter insertion.

A non-contrast abdominal computed tomography scan showed normal kidney size and appearance without hydronephrosis. The liver was normal size with sharp borders. The patient was treated with intravenous fluids, inotropic support, and intravenous antibiotics. Despite these interventions, he remained anuric with worsening hyperkalemia, necessitating urgent hemodialysis.

Within 10 minutes of initiating hemodialysis, a yellowish discoloration appeared in the effluent tubing of the dialysate. Simultaneously, the dialyzer fibers, which are typically pinkish in color, began to develop a yellowish tint. By the end of the session, the dialyzer appeared distinctly yellow, likely due to bilirubin deposition [Figure 1A–1C].

Sinus of Valsalva aneurysms (SVA) are uncommon cardiac anomalies. They represent only 0.1–3.5% of congenital heart defects. While rupture of an SVA can lead to acute left-to-right shunting and heart failure, its association with chromosome 22q11.2 deletion (DiGeorge syndrome) has rarely been documented.

Transthoracic echocardiography (TTE) revealed a continuous systolic-diastolic jet suggestive of aortic-to-right-atrial communication. TEE and contrast-enhanced computed tomography (CT) confirmed rupture of a right-coronary-cusp SVA into the right atrium. The patient underwent urgent surgical repair. Initial direct-suture closure was unsuccessful because of persistent flow and was converted to definitive pericardial-patch repair. Postoperative TTE demonstrated complete closure and preserved biventricular function. To the best of our knowledge, this case represents only the third known example of ruptured SVA in a patient with DiGeorge syndrome. It underscores the expanding cardiovascular phenotype of 22q11.2 deletion and highlights the role of multimodality imaging and timely surgical intervention.

Genitourinary syndrome of menopause (GSM) has gained increasing attention in recent years, with growing literature on its pathophysiology, clinical presentation, and treatment options. A bibliometric analysis helps identify high-quality research based on citation rates and journal impact factors. In this review, our objective was to analyze the key themes and topics in GSM literature. We conducted a bibliometric analysis using the Thomson Reuters Web of Science database to identify the top 100 most-cited articles on GSM published over the past 50 years. Data were categorized into manuscript type, theme, author, country of origin, journal impact factor, and citation rate. The mean citation count per article was 67, ranging from 405 to 5. The most-cited paper, authored by the North American Menopause Society, had the highest citation rate of 45.0 citations per year. The majority of articles (n=65) were published between 2010 and 2019. Randomized controlled trials comprised the largest publication type (29%). Most articles (n=65) were published in Q1-ranked journals. Although GSM is a relatively recent concept, the most-cited articles from the past 50 years generally focus on its medical and surgical treatments, as well as its epidemiology. This bibliometric analysis is the first to evaluate the top 100 most influential publications on GSM.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a wide spectrum of clinical severity. The gold standard diagnosis of infection is reverse transcription polymerase chain reaction of nasopharyngeal swabs, which also provides a semiquantitative assessment of viral loads by measuring cycle threshold (CT) values.

Objective: To assess whether CT values at admission can predict mortality and oxygen needs among individuals hospitalized for coronavirus disease 2019 (COVID-19).

Methods: The retrospective study included adults hospitalized for COVID-19 between 1 August 2020 and 30 April 2021 at Barzilai University Medical Center. Patients were categorized according to initial CT values as high (≥ 25) or low (< 25) values. The primary outcome was the association between CT values during admission and overall mortality.

Results: The study group included 636 patients, with a mean age of 67.2 years, 54.4% males. Overall mortality of patients with CT values < 25 was significantly higher (odds ratio for mortality 1.78 vs. patients with CT ≥ 25, P = 0.002). Significantly more patients in the low CT group required oxygen support than in the high CT group, 50% vs. 31.9% (P < 0.001). An inverse association between CT values and mortality rates remained significant in multivariate regression analysis, such that a 1-unit decrease in CT was associated with a 6% increased mortality.

Conclusions: Lower CT values at admission were associated with increased mortality among patients hospitalized for COVID-19. CT values can be used to predict outcomes among such patients.

Background: Antiphospholipid syndrome (APS) is a common form of acquired thrombophilia associated with a high thrombotic risk. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (GLA) gene and presents with a wide range of clinical manifestations, including a high rate of thrombosis. Previously reported, 45% of FD patients were found to have antiphospholipid autoantibodies.

Objectives: To determine the prevalence of FD in patients with APS.

Methods: We conducted a prospective study. Data were collected from 41 APS patients at our outpatient clinic at Meir Medical Center in Israel. We utilized chemical and genetic analyses to identify FD among APS patients. Dried blood spot (DBS) was used to assess GLA activity in males, and mutational analysis of the GLA gene was performed by sequencing exons and their flanking regions in women.

Results: Among 41 antiphospholipid patients, one male patient was diagnosed with FD. Gal variants were not detected in any of the tested female patients.

Conclusions: We found a low prevalence (2.4%) of FD in APS patients. Larger studies are needed to evaluate the clinical utility and cost-effectiveness of routine FD screening in this population.

Immune thrombocytopenia (ITP), driven by autoantibodies targeting platelet antigens, is an acquired disorder posing considerable challenges, particularly in pregnancy, where its prevalence escalates to 1–3 per 10,000 women, a tenfold increase compared to the general population [1]. Predominantly characterized by a heightened risk of bleeding, particularly during pregnancy, the incidence of significant hemorrhagic events stands at approximately 18%, mostly non-severe [1]. Despite its rarity, thrombosis can manifest as a complication, especially when accompanied by antiphospholipid antibodies, which amplify the propensity for arterial and venous thrombotic events alongside obstetric complications and thrombocytopenia [2,3].

In this case report, we present the case of a young female with primary unexplained infertility, complicated by ITP and antiphospholipid syndrome (APS), predisposing her to increased bleeding and thrombotic risks. During a multidisciplinary consultation, the medical staff navigated the intricate landscape of fertility treatments and pregnancy options, carefully considering the delicate balance between risks and benefits to optimize patient outcomes.

Background: Behcet's syndrome (BS) is a multisystem syndrome that typically manifests as recurrent oral and genital ulcers, as well as other systemic manifestations. Few studies describing the characteristics of BS among Israeli patients have been published.

Objectives: To describe the characteristics of BS patients and to compare Jewish and Arab subpopulations.

Methods: We retrospectively reviewed electronic medical records and extracted demographic, clinical, laboratory, and medication data for each patient. We compared the Jewish and Arabic BS patients.

Results: The cohort included 98 patients. Males constituted 49 (50%); mean age at the time of diagnosis was 29.9 years; 71 (72.4%) were Arab and 27 (27.6%) were Jewish. Oral ulcers were evident in 93 patients (94.9%) and genital ulcers in 54 (55.1%). Involvement of the skin, joints, eyes, gastrointestinal tract, and neurologic and vascular systems were demonstrated among 42 (42.9%), 57 (58.2%), 47 (48.0%), 8 (8.2%), 10 (10.2%), and 15 (15.3%), respectively. HLA B51 was positive in 24 of 37 (64.9%). Pathergy was positive in 8 of 12 (66.7%). Colchicine was used in 82 (83.7%), azathioprine 47 (48%), methotrexate 16 (16.3%), apremilast 10 (10.2%), cyclosporine-A 8 (8.2%), adalimumab 26 (26.5%), infliximab 12 (12.2%), cyclophosphamide 1 (1.0%), tocilizumab 2 (2.0%), and anti-coagulation 6 (6.1%). The Arab and Jewish subpopulations were significantly different regarding male proportion, 40 (56.3%) vs. 9 (33.3%), P = 0.042.

Conclusions: BS is more common among Arabs in northern Israel, but no significant clinical or demographic differences were found except for a higher proportion of male patients among Arabs.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract, with an estimated prevalence of 1 in 100,000 individuals. While most cases follow an autosomal dominant inheritance pattern, some are caused by de novo mutations [1].

The age of onset for JPS is typically during childhood or adolescence, with a mean age at diagnosis of 18.5 years [2]. A major concern in JPS is the increased risk of colorectal cancer (CRC), requiring close lifelong surveillance. The cumulative lifetime risk for CRC ranges from 38% to 68%, with a mean age at diagnosis between 34 and 44 years [3].

Although juvenile polyps were initially considered to have low malignant potential, studies have identified two pathways of carcinogenesis in JPS: progression from hamartomatous polyps to adenoma and then to adenocarcinoma or direct transformation of hamartomatous polyps into adenocarcinoma. The management of JPS is tailored to each patient's specific manifestations and clinical presentation. The primary treatment goal is to prevent morbidity associated with gastrointestinal polyps, such as bleeding and intestinal obstruction.

Background: Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare form of ectodermal dysplasia caused by biallelic mutations in NECTIN4 (PVRL4) gene.

Objectives: To identify new and rare mutations of the NECTIN4 gene in two unrelated families with EDSS.

Methods: Six patients from two unrelated families were diagnosed with EDSS. Next generation sequencing and Sanger sequencing were performed on DNA extracted from peripheral blood from affected and unaffected individuals from the families. We performed a literature search to identify previously reported cases of EDSS.

Results: A homozygous c.680A>G p.His227Arg mutation in NECTIN4 was found in five affected members of both families. One patient was found to be compound heterozygous for the latter mutation and for another novel missense mutation in NECTIN4 (c.79+1G>A). Both mutations affect the extracellular domain of nectin-4. A literature search identified only 13 reported families affected by this rare disorder.

Conclusions: We described two families with six affected members presenting with EDSS caused by two novel NECTIN4 mutations. We also reviewed the current available data on EDSS in the medical literature.

A 71-year-old man with a history of hypertension, type 2 diabetes mellitus, and dyslipidemia was admitted for unstable angina. He subsequently underwent coronary angiography. Approximately 2 hours after successful percutaneous coronary intervention (PCI), he reported a burning and itching sensation on his buttocks. The patient had no history of atopy or drug hypersensitivity. Physical examination revealed a bilateral erythematous, warm, tender, blistering rash localized to his buttocks [Figure 1A].

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.