Israel Medical Association Journal

Background: The Agatston coronary artery calcium (CAC) score is a decision-guiding aid for risk assessment and personalized management in the primary prevention of atherosclerotic cardiovascular disease.

Objectives: To explore the real-life clinical experience of CAC testing by characterizing its indications, significance of scores, and corresponding lipid-lowering treatments.

Methods: A retrospective descriptive study of patients treated at the lipids clinic at Rabin Medical Center (Beilinson Campus), who underwent CAC score evaluation between 2017 and 2022 was conducted. The data collected from electronic medical files included demographics, co-morbidities, indications for the test, CAC score levels, and the recommended therapeutic regimen.

Results: The study cohort included 88 patients. The main indication was assessment of the existence of atherosclerosis in cases where there was no clear indication for lipid lowering treatment (65, 74%). In most patients, there was no evidence of atherosclerosis (CAC = 0 AU, n=30) or only mild disease (CAC=1–99 AU, n=35). As the CAC score increased, more patients were prescribed lipid lowering treatments, from very few prescriptions in those with a CAC score of 0 AU and almost 100% among those with score of ≥ 400 AU. The factors that predicted CAC > 0 AU were male sex and older age.

Conclusions: CAC scores should be used more often to determine risk assessment. Further analysis of the implications of scores between 0–400 AU is needed.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition. Accumulated research and data since 2003 have increasingly affirmed its classification as a systemic disease. Although IgG4-RD generally presents with involvement of one or several organ systems, it can affect almost any organ. The disease manifests gradually with the development of tumor-like lesions.

Constitutional symptoms, such as systemic fever and elevated inflammatory markers, are generally absent in association with this pathological condition. However, it is common for patients to exhibit allergy characteristics in addition to a slight increase in peripheral blood eosinophilia. The clinical manifestations of the disease exhibit variability on the specific organ system affected. Specific involvement of organs can ultimately result in organ failure. For example, retroperitoneal fibrosis commonly leads to post-renal failure [1]. The 2020 Revised Comprehensive Diagnostic (RCD) criteria for IgG4-RD include three components for diagnosis: clinical and radiological components (1), serological diagnosis (2), and unique pathological diagnosis (3). When all three are present it is a definitive diagnosis. The presence of components 1 + 3 constitutes a probable diagnosis, while the presence of components 1 + 2 indicates possible diagnosis [2].

Testicular involvement of IgG4-RD has been described in a few case reports. However, the uniqueness of our case is the manifestation of a testicular mass as a different target organ of relapse in a patient in remission from retroperitoneal fibrosis.

Background: The coronavirus disease 2019 (COVID-19) pandemic posed significant challenges to healthcare systems worldwide, including a surge in the use of extracorporeal membrane oxygenation (ECMO).

Objectives: To compare outcomes and costs of COVID-19 and non-COVID-19 adult patients treated with ECMO in the intensive care unit (ICU) at Tel Aviv Sourasky Medical Center.

Methods: We conducted a retrospective study. Clinical outcomes, ECMO duration, ICU and hospital length of stay (LOS), and healthcare costs were examined and compared between the two groups.

Results: A total of 119 patients were treated with ECMO between 2016 and 2023; 56 (47.1%) diagnosed with COVID-19. The study found no significant difference in mortality rates between COVID-19 and non-COVID-19 patients. However, COVID-19 patients experienced significantly longer ECMO durations and ICU LOS. Hospitalization and ECMO operation costs were notably higher for COVID-19 patients, but overall admission costs were lower compared to non-COVID-19 patients, with cost of surgical interventions, consultations and imaging contributing to the price gap.

Conclusions: Despite longer durations of ECMO and LOS, the economic burden of ECMO in COVID-19 patients was significantly lower than non-COVID-19 patients. Strict patient selection should be utilized, a fortiori during times of surge-capacity.

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.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

The prevalence of difficult-to-treat rheumatoid arthritis (D2T RA) varies between 5% and 25%, with females comprising the majority of patients and no difference in patient age between D2T and non-D2T RA cohorts. While several attempts to subclassify D2T RA patients into defined subgroups have been tried, the inclusion of an individual D2T RA patient to one of the predefined subgroups can be difficult or impossible as multiple factors are usually involved in the mechanisms of rheumatoid arthritis (RA) refractoriness, with the complex interplay of inflammatory, structural, social, and psychological factors being unique for each patient. More severe disease at presentation, including seropositivity and early erosion formation, and insufficiently aggressive initial treatment can both contribute to the eventual development of D2T RA. No single test or study can replace the holistic clinical approach to the diagnosis and understanding of the causation of D2T RA. Traditional in-depth clinical history and thorough clinical examination remain sine qua non in managing D2T RA patients. Multifaceted contributions of inflammatory and non-inflammatory components create the uniqueness of D2T RA and dictate a comprehensive approach to the management, including both pharmacologic and non-pharmacological therapeutic strategies. Mean annual total costs for D2T RA patients have been estimated as being about twice as high as that of patients with non-D2T RA.

Background: Data regarding the management of adnexal torsion (AT) during the coronavirus disease 2019 (COVID-19) pandemic are scarce.

Objectives: To study the effects of actions to limit the spread of COVID-19 on AT management.

Methods: We conducted a retrospective cohort study of all women who underwent laparoscopy for suspected AT between March 2011 and February 2021. We compared the COVID-19 pandemic period, (15 March 2020–2 August 2021, group A) to a parallel period (2019–2020, group B), and a 9-year period preceding the pandemic (March 2011–February 2020, group C).

Results: We performed 97 laparoscopies in group A, 82 in group B, and 635 in group C. The proportion of women presenting following in vitro fertilization treatment was lower (odds ratio [OR] 0.22, 95% confidence interval ]95%CI] (0.06–0.86), P < 0.023). Time from admission to decision to operate was shorter (2.7 vs. 3.9 hours, P = 0.028) in group A than group B. Time from admission to surgery was shorter (9.1 vs. 12.5 hours, P = 0.005) and the rate of surgically confirmed AT was lower (59 [60.8%] vs. 455 [71.7%], P = 0.030, OR 0.61, 95%CI 0.39–0.95) in group A than group C. Among surgically confirmed AT cases only, mean time from admission to decision was shorter in group A than group B (2.6 vs. 4.6 hours, P = 0.014).

Conclusions: We identified differences in time from admission to clinical decision and from admission to surgery among women with suspected AT during the COVID-19 pandemic.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune demyelinating disorder of the central nervous system. Optic neuritis (ON) is the most common clinical manifestation of MOGAD in adults. In 2023, new MOGAD diagnostic criteria were proposed, highlighting the importance of supplemental criteria when MOG-immunoglobulin G (IgG) titers are unavailable.

Objective: To investigate the applicability of the 2023 MOGAD criteria in patients diagnosed with MOGAD and treated before the availability of MOG-IgG titers.

Methods: We conducted a retrospective chart review of patients classified as MOGAD between 2010 and 2023 at Rabin Medical Center. Patient demographics as well as clinical and imaging data were collected, including visual acuity, expanded disability status score, core demyelinating events, antibody status, and brain and optic nerve magnetic resonance imaging data. Patients fulfilling the 2023 MOGAD criteria were reported as definite MOGAD.

Results: Fifteen patients met the 2023 MOGAD diagnostic criteria despite lack of MOG-IgG titer. The most common supplemental criterion meeting the 2023 MOGAD criteria was optic disc edema (n=12, 80%), followed by longitudinal optic nerve involvement (53%), bilateral ON (40%), and perineural optic sheath enhancement (33%).

Conclusions: All patients with a clinical diagnosis of MOG-ON in our cohort fulfilled the 2023 MOGAD criteria despite the lack of antibody titers. The 2023 MOGAD criteria can be reliably applied to Israeli cohorts, prior to availability of MOGAD IgG titers, with particular attention to additional supplemental criteria. Since the 2023 MOGAD criteria were published, MOGAD IgG titers have been added to routine testing at our facility.

The issue of genital ulcers (GUs) in Israeli Arab female patients with Behçet's disease (BD is important as GUs are considered a unique feature of BD and stand as diagnostic criterion for the diagnosis in the International Study Group (ISG) criteria [1] and the International Criteria for Behcet Disease (ICBD) [2]. According to the ISG, GUs can be detected by a physician or by the patient [1]. While oral ulcers are easily observable, the identification of more hidden GUs pose a significant challenge.

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: 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.

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: 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.

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.

Since the introduction of the international study group (ISG) criteria for the diagnosis of Behçet's disease (BD) in the early 1990s by Yazici and colleagues [1] and the international criteria for BD (ICBD) by Davatchi and colleagues in 2014 [2], great progress has been achieved in the diagnosis of BD with fairly high sensitivity and specificity rates. However, a small, but very challenging and unique minority might not fulfill these criteria, at least at presentation. These patients are most challenging as they may present with life-threatening vascular or neurological manifestations. If the diagnosis BD is delayed, the risk for morbidity and even mortality might be increased. Therefore, we should aim for early diagnosis and prompt treatment.