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: Gram-negative bloodstream infections (GN-BSI) are life threatening. Appropriate antimicrobial therapy and source control when indicated improve survival. Dementia is an independent risk factor for death and is associated with increased risk for infections, especially in advanced stages. Data about the best diagnostic and therapeutic approaches for patients with dementia and GN-BSI are lacking.

Objectives: To evaluate patients with dementia and GN-BSI and determine whether diagnostic imaging improves clinical outcomes.

Methods: We performed a retrospective cohort study of adult patients with GN-BSI, during 2019–2022. Patients with or without a diagnosis of dementia were compared. Outcomes were in-hospital mortality and recurrent bacteremia. Demographic, clinical, diagnostic, and therapeutic data were collected and analyzed.

Results: A total of 87 patients with dementia and 130 without were included. Patients with dementia received appropriate empirical antimicrobial therapy in 38% of cases compared to 62% of patients without dementia, P < 0.001. Imaging studies were performed in half of patients in both groups. In the dementia group, 17% had abnormal findings that required source control versus 30% in the control group (P = 0.049). Source control was performed in 15% of patients with dementia versus 28% of patients without dementia (P = 0.032). Mortality was 27.6% in the dementia group versus 22.3% in the control group (P = 0.42).

Conclusions: In patients with dementia and GN-BSI, imaging studies have lower effect on clinical outcomes. Imaging studies should be performed in selected cases only and not conducted routinely.

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: Cardiac implantable electronic devices (CIEDs) are increasingly being used; thus, there is an increasing need for transvenous lead extraction (TLE).

Objectives: To summarize our experience with TLE at single referral center in northern Israel.

Methods: The study included all patients who underwent TLE at our center between 2019 and 2022, regardless of the indication.

Results: The cohort included 50 patients. The mean age was 69 ± 10.36 years; 78% were males. A total of 99 electrodes were targeted. The mean number of electrodes was 1.96 (range 1–4) per patient. The time between lead implantation and extraction ranged between 1.1 and 34 years with an average of 8.14 ± 5.71 years (median of 7.5 years). Complete lead removal was achieved in 98% of patients and in 98.99% of leads. The complete procedural success rate as well as the clinical procedural success rate was 96%. The procedural failure rate was 4% (1 patient died 2 days after the index procedure and 1 patient remained with large portion of lead). The indication for TLE was infection in 78% of the cohort group. Powered mechanical sheaths were used in 36 patients (72%), laser sheaths in 27 (54%), and a combination of laser and mechanical sheaths in 16 (32%).

Conclusions: The clinical and procedural success rates of TLE, primarily for CEID-related infection, were high. A combination of laser and mechanical sheaths was needed in one-third of patients.

Background: Long-term support with a HeartMate 3 (HM3) left ventricular assist device (LVAD) has improved outcomes of patients with end-stage heart failure. However, there is a paucity of data on the outcomes of patients who underwent concomitant cardiac surgical procedure (CCSP) during HM3-LVAD implantation.

Objectives: To assess our single-center experience with patients who underwent CCSP during the implantation of an HM3-LVAD.

Methods: From December 2016 until April 2022, 131 adult patients underwent HM3-LVAD implantation. A total of 23 patients underwent CCSP during the HM3-LVAD implantation+CCSP, and 108 underwent only HM3-LVAD implantation (HM3-only).

Results: The median age was 59 ± 11 years (range 54-67), 82% (n=108) were male, and 76% (n=100) were implanted as a bridge-to-transplant. The concomitant procedures performed during the implantation included 8 aortic valve repairs/replacements, 14 tricuspid valve repairs, 4 patent foramen ovales or atrial septal defect closures, and 3 other cardiac procedures. The mean cardiopulmonary bypass time was 113 ± 58 minutes for the HM3-only group and 155 ± 47 minutes for the HM3+CCSP group (P = 0.007). The mortality rates at 30 days, 6 months, and 12 months post-implantation were 2 (9%), 5 (22%), and 6 (26%) respectively for the HM3+CCSP group, and 7 (6%), 18 (17%), and 30 (28%) for the HM3-only group (P = 0.658, 0.554, and 1.000).

Conclusions: Our experience demonstrated no significant difference in the 30-day, 6-month, and 12-month mortality rates for patients who underwent a CCSP during HM3-LVAD implantation compared to patients who did not undergo CCSP during HM3-LVAD implantation.

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.

Background: Pyogenic flexor tenosynovitis (PFT) is a common and severe hand infection. Patients who present early can be treated with intravenous antibiotics.

Objectives: To determine whether PFT caused by animal bites and treated with antibiotics leads to a different outcome than other disease etiologies due to the extensive soft tissue insult and different bacterial flora.

Methods: We conducted a retrospective cohort study of 43 consecutive patients who presented with PFT between 2013 and 2020. The 10 patients who presented with PFT following an animal bite were compared to those who presented with PFT caused by any other etiology.

Results: Patients who were bitten pursued medical attention sooner: 1.9 ± 1.4 days compared with 5.3 ± 4.7 days (P = 0.001). Despite the quicker presentation, patients from the study group received similar antibiotic types and duration as controls. All patients were initially treated with intravenous antibiotics under surveillance of a hand surgeon. One patient (10%) from the study group and four controls (12%) were treated surgically (P = 1). Average follow-up was 17 ± 16 days. At the end of follow-up, one (10%) patient from the study group and three (9%) controls sustained mild range of motion limitation and one (3%) patient from the control group had moderate limitations (P = 0.855).

Conclusions: Intravenous antibiotic treatment, combined with an intensive hand surgeon follow-up, is a viable option for the treatment of PFT caused by animal bites.

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].

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism and manifests as a multisystem disease. Most patients present with oropharyngeal malformations, cardiomyopathies, elevated liver enzymes, and hypoglycemia. Treatment with D-galactose has been shown to improve symptoms. Our patient presented with PGM1 deficiency. She conceived spontaneously. Throughout her pregnancies, our patient was monitored by a multidisciplinary team of cardiologists, endocrinologists, and physicians with experience in high-risk pregnancy. She delivered twice by cesarean section. Our case highlights the importance of a multidisciplinary approach and individualized management of prenatal and postpartum care of a patient with a PGM1 deficiency. To the best of our knowledge, there have been no reports about a PGM1-deficient patient who conceived and delivered.

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].

Hearing and vestibular function may be affected by gout and/or hyperuricemia. We performed a systematic review of the literature on ear involvement in patients with gout and hyperuricemia. We selected 24 articles: 8 case reports and 16 original articles. Case reports mainly focused on the presence of tophi in the middle ear, which was resolved with surgical treatment. Seven articles studied the hearing function in relationship to serum uric acid and 10 articles studied the occurrence of vertigo, with one of them studying both aspects. Regarding results on vertigo, five studies showed an association with uric acid elevation, three with lowering of uric acid, and two found no differences. Concerning hearing loss, five studies detected poor hearing function in association with high uric acid levels while other two did not.) Most of the studies showed an association of hearing loss with high uric acid/gout. Regarding vestibular function, the results are too heterogeneous to make any conclusions.