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.

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.

Background: Hip fractures are a public health problem that disproportionately affects the elderly. Displaced femoral neck fractures were treated historically with hemiarthroplasty, but the use of total hip arthroplasty (THA) is increasing showing superior long-term results.

Objectives: To assess whether THA has superior short-term results compared to bipolar hemiarthroplasty for displaced femoral neck fractures.

Methods: Two groups of active older patients underwent either cementless bipolar hemiarthroplasty or THA for displaced femoral neck fracture. All patients were operated on using the direct lateral approach to the hip joint. Patients were assessed using the Harris Hip Score at hospital discharge and at 6 weeks follow-up.

Results: We included 40 patients ages 65–85 years; 18 underwent bipolar hemiarthroplasty and 22 THA. The number of women in each group was similar, as was mean age: 73.1 ± 4.2 years in the hemiarthroplasty group and 71.0 ± 3.7 in THA. Harris Hip Score on hospital discharge was similar in both groups. Walking ability at discharge was better in the THA cohort and they were discharged sooner: 5.2 ± 1.3 vs. 6.4 ± 1.7 days following hemiarthroplasty (P = 0.021). At 6 weeks follow-up, the mean Harris Hip Score was higher in the THA group (78.6 ± 11 vs. 61.5 ± 17 for hemiarthroplasty, P < 0.001). Patients in the THA group walked longer distances, needed less support while walking, and reported less pain.

Conclusions: Better short-term results at hospital discharge and at 6 weeks follow-up after THA contributed to earlier patient independence and shorter hospital stays.

Background: With age, colorectal cancer (CRC) prevalence rises. The elderly (> 75 years), and the very elderly (> 85 years) are especially vulnerable. The advantages of screening must be assessed in the context of diminished life span and co-morbidities.

Objective: To compare CRC findings in colonoscopies that were performed following a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) in both elderly and very elderly age groups with those of younger patients.

Methods: We identified colonoscopies conducted between 1998 and 2019 following a positive stool test for occult blood in asymptomatic individuals. A finding of malignancy was compared between the two patient age groups. Furthermore, a sub-analysis was performed for positive malignancy findings in FOBT/FIT among patients > 85 years compared to younger than < 75 years.

Results: We compared the colonoscopy findings in 10,472 patients: 40–75 years old (n=10,146) vs. 76–110 years old (n=326). There was no significant difference in prevalence of CRC detection rate between the groups following positive FOBT/FIT (2.1% vs. 2.7%, P = 0.47). Similar results for non-significant differences were obtained in the sub-analysis compared to malignancy detection rates in the very elderly 0% (n=0) vs. 2.1% for < 75 years old (n=18), P = 0.59.

Conclusions: Although the prevalence of CRC increases with age, no significant increase in the detection rate of CRC by FOBT was found in either the elderly or very elderly age groups. Screening colonoscopies in elderly patients should be performed only after careful consideration of potential benefits, risks, and patient preferences.

Celiac disease (CD) is an immune-based reaction to dietary gluten. CD can present with a diverse array of symptoms. Many CD patients have no symptoms at all. Thus, a great number of atypical cases of CD remain undiagnosed, leading to a risk of long-term complications. Some atypical symptoms of CD such as pregnancy complications, infertility, recurrent abortions, intrauterine growth restriction, preterm delivery, and severe preeclampsia have been investigated in undiagnosed and diagnosed pregnant women with CD. Nutrient deficiency and autoimmune pathogenic mechanisms have been hypothesized to be the explanation of these adverse pregnancy outcomes. Recently, an association between obstetric complications and anti-tissue transglutaminase antibodies titers in women with CD has been reported. While the adverse effects of CD on the reproductive system are well investigated, there are only a few reports in the literature on the effect of pregnancy and puerperium on CD. We reviewed the published literature on the adverse effects and pathophysiology of CD in reproductive disorders and the effect of pregnancy and puerperium on the manifestation of CD.

Background: Unfractionated heparin is the preferred anticoagulant used during open heart surgeries, including left ventricular assist device (LVAD) implantation. In cases in which patients are heparin-induced thrombocytopenia positive (HIT+), the accepted practice has been to substitute heparin with bivalirudin. This practice may be associated with significant bleeding and adverse outcomes.

Objectives: To review our experience with HIT+ patients who were heparin-induced thrombocytopenia with thrombosis negative (HITT-) and who underwent HeartMate 3 LVAD implantation using heparin intraoperatively rather than bivalirudin.

Methods: From 2016 to 2022, 144 adult patients were implanted with HeartMate 3 LVAD at our center. Among them, 7 were detected as HIT+ but HITT- and therefore were prescribed intraoperatively with heparin and treated pre- and postoperatively with bivalirudin. We reviewed the preoperative, intraoperative, and postoperative characteristics as well as short-term mortality and the complication rates of these HIT+ patients.

Results: The median age of our cohort was 56 years (51–60), 71% were male (n=5), all were INTERMACS Level 1, and most were bridged to transplant (n=6, 86%). The 30-day mortality rate post-implantation was 0%. The average 24-hour chest drain postoperative output was 1502.86 ± 931.34 ml. There were no intraoperative pump thromboses, perioperative thromboses, cerebrovascular accidents, or gastrointestinal bleeding within the first 24 hours postoperative. One patient required a revision due to bleeding.

Conclusions: Intraoperative unfractionated heparin may be administered to patients who are HIT+ and HITT- while undergoing LVAD implantation. However, further investigation is required.

Background: In 2019, 1 mg subcutaneous semaglutide was registered for the treatment of diabetes in Israel. Recognition of its effect on weight has led to its use as a treatment for obesity.

Objectives: To explore physicians’ pre-therapy considerations, therapy practices, and attitudes regarding subcutaneous semaglutide for weight loss.

Methods: A 22-item questionnaire was disseminated to physicians who prescribed semaglutide 1-mg for weight loss using an authorized off-label path.

Results: In total, 127 physicians completed the questionnaire. As for pretreatment requirements, in the absence of diabetes, 30% requested a minimal body mass index of 30 kg/m². Additional requirements were documented lifestyle-change effort (67%) and prior weight loss medication use (13%). Half of the physicians regarded calorie restriction, and 23% considered physical activity as necessary for weight loss while on therapy. As for dose, most physicians (78%) started with a 0.25-mg weekly injection, 57% doubled the dose monthly, and all others recommended doubling when side effects subsided. Regarding weight loss goal, 43% of the physicians set a personal goal with each patient while 26% limited the goal to 10% of initial weight. Fewer than 50% of physicians discussed treatment duration with their patients, and 52% of patients discontinued therapy in the first 3 months. The main reasons for discontinuation were price, lack of effect, and fear of long-term side effects.

Conclusions: The diverse approaches regarding off-label use of semaglutide for weight reduction highlight the necessity to guide physicians and standardize treatment regimen.

Background: During combined phacovitrectomy, it is common practice to suture the main corneal incision to prevent intraoperative and postoperative wound leak. However, it may be possible to avoid suturing using a self-sealing corneal incision technique as in standard cataract surgery.

Objectives: To evaluate the clinical outcome, safety, and complications of combined phacovitrectomy without preventive suturing.

Methods: This retrospective case series study included consecutive patients who underwent combined phacovitrectomy between January 2018 and June 2019 for mixed indications. Surgeries were performed at a tertiary university hospital. All surgeries were performed by the same two retinal surgeons. Cataract surgery was performed first, followed by insertion of trocars and vitrectomy. Corneal sutures were not planned but were used at the discretion of the surgeon.

Results: The cohort included 106 eyes of 102 patients. Suturing of the main corneal incision was deemed necessary in five cases (5%) because of a main incision leak or anterior chamber shallowing during trocar insertion. No other complications related to the absence of prophylactic corneal sutures were encountered during surgery or follow-up.

Conclusions: Preventive corneal suturing may not be necessary in combined phacovitrectomy surgery and can be used in the few cases in which it is indicated during surgery.

Migraine is very common headache disorder, usually starting at a young age with a higher prevalence in females. In this narrative review, we summarize the prevalence, burden, and socio-demographic characteristics of migraineurs worldwide and specifically in Israel. We searched standard electronic bibliographic databases, including MEDLINE (via PubMed), Embase, Google Scholar, and Up to Date using combinations of search terms and reviewed the articles we found. The factors reviewed included prevalence and incidence, burden, sex differences, age distribution, cognitive function, socioeconomic status, religion, country of origin, and urban vs. rural dwelling.

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

Background: Perianal abscesses require immediate incision and drainage (I&D). However, prompt bedside drainage is controversial as it may compromise exposure and thorough anal examination.

Objectives: To examine outcomes of bedside I&D of perianal abscesses in the emergency department (ED) vs. the operating room (OR).

Methods: We conducted a retrospective review of all patients presented to the ED with a perianal abscesses between January 2018 and March 2020. Patients with Crohn’s disease, horseshoe or recurrent abscesses were excluded.

Results: The study comprised 248 patients; 151 (60.89%) underwent I&D in the OR and 97 (39.11%) in the ED. Patients elected to bedside I&D had smaller abscess sizes (P = 0.01), presented with no fever, and had lower rates of inflammatory markers. The interval time from diagnosis to intervention was significantly shorter among the bedside I&D group 2.13 ± 2.34 hours vs. 10.41 ± 8.48 hours (P < 0.001). Of patients who underwent I&D in the OR, 7.3% had synchronous fistulas, whereas none at bedside had (P = 0.007). At median follow-up of 24 months, recurrence rate of abscess and fistula formation in patients treated in the ED were 11.3% and 6.2%, respectively, vs. 19.9% and 15.23% (P = 0.023, 0.006). Fever (OR 5.71, P = 0.005) and abscess size (OR 1.7, P = 0.026) at initial presentation were risk factors for late fistula formation.

Conclusions: Bedside I&D significantly shortens waiting time and does not increase the rates of long-term complications in patients with small primary perianal abscesses.