Israel Medical Association Journal

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by an inadequate attenuation of the cytotoxic and innate immune system resulting in uncontrolled inflammation in multiple organ systems. Predominant clinical findings include fever, cytopenia, and hepatosplenomegaly [1].

Infectious diseases are a well-documented trigger of HLH, with viral infection being the most common cause. Less commonly, HLH has also been reported in the setting of bacterial infections, with rare cases described secondary to rickettsial diseases [1]. In this report, we present a case of HLH in the setting of bacterial infection with Rickettsia typhi, murine typhus.

Background: The coronavirus disease 2019 (COVID-19) pandemic showed the need to evaluate disease severity promptly at the time of hospital admission. 

Objectives: To establish an admission protocol, which included clinical and laboratory findings. 

Methods: We conducted a retrospective study at Wolfson Medical Center, Israel, for a period of 19 months (2020–2021). We established a protocol for patients who were admitted with COVID-19 infection. The protocol parameters included demographic data, co-morbidities, immune status, oxygen level at room air on admission, oxygen demand, lymphopenia, C-reactive protein (CRP) level, lactate dehydrogenase, D-DIMER, creatinine, aspartate transferase, alanine aminotransferase, and ferritin. Based on this protocol, we defined the severity of COVID-19 at the beginning of hospitalization and started treatment without delay. This protocol included ferritin levels as a guide to severity and outcome of patients. A database was established for all the parameters of the patients included in the study. 

Results: The study included 407 patients; 207 males (50.9%), 200 females (49.1%). The age range was 18–101 years. Hyperferritinemia (> 1000 ng/dl) was one of the strongest and most significant predictors for severe disease in these patients (P < 0.001). Lymphopenia, high levels of CRP, alanine aminotransferase, aspartate transferase, lactate dehydrogenase, and creatinine also correlated with severe disease, complications, and death. 

Conclusions: Abnormal ferritin levels were a very significant and clear indicator of the development of severe COVID-19. The addition of ferritin levels to our protocol aided in finding which patients were at increased risk for morbidity and mortality.

Background: Prognostication is complex in patients critically ill with coronavirus disease 2019 (COVID-19).

Objectives: To describe the natural history of ventilated critical COVID-19 patients.

Methods: Due to our legal milieu, active withdrawal of care is not permitted, providing an opportunity to examine the natural history of ventilated critical COVID-19 patients. This retrospective cohort included COVID-19 ICU patients who required mechanical ventilation. Respiratory and laboratory parameters were followed from initiation of mechanical ventilation for 14 days or until extubation, death or tracheostomy.

Results: A total of 112 patients were included in the analysis. Surviving patients were younger than non-survivors (62 years [range 54–69] vs. 66 years [range 62–71], P = 0.01). Survivors had a shorter time to intubation, shorter ventilation duration, and longer hospital stay. Respiratory parameters at intubation were not predictive of mortality. Nevertheless, on ventilation day 10, many of the ventilatory parameters were significantly better in survivors. Regarding laboratory parameters, neutrophil counts were significantly higher in non-survivors on day 1 and C-reactive protein levels were significantly lower in survivors on day 10. Modeling using a generalized estimating equation showed small dynamic differences in ventilatory parameters predictive of survival.

Conclusions: In ventilated COVID-19 patients when there is no active care withdrawal, prognostication may be possible after a week; however, differences between survivors and non-survivors remain small.

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on patient populations can be divided to direct consequences of the disease and indirect implications of changes imposed on the national healthcare systems. The impact of the later survival of chronic hemodialysis patients is still unknown.

Objectives: To examine the impact of quarantine on health outcomes of dialysis patients.

Methods: In a retrospective case-controlled study, we compared chronic hemodialysis patients from two separate timeframes: during a quarantine period and a parallel time without quarantine.

Results: The study included 344 hemodialysis patients. Baseline characteristics were compared between those enrolled in 2015 and those enrolled in 2020. Despite comparable clinical parameters, a statistically significant increase in the 6-month mortality rate was observed in 2020 (1.2% vs. 6.7%, P = 0.01), primarily attributed to sepsis. Notably, no deaths were attributed to COVID-19 in 2020. Interdialytic weight gain and dialysis quality remained similar between the two groups, with a mild trend toward excessive weight gain in 2020. Secondary outcomes after 6 months did not significantly differ, except for lower sodium values in 2015 compared to 2020.

Conclusions: Dialysis patients experienced disproportionate effects from the COVID-19 pandemic, even with continuous care and no direct virus-related fatalities. The findings showed unintended consequences of quarantine measures, highlighting adverse impact on both physical and mental health. Recognizing and addressing these consequences are imperative for minimizing their impact in future pandemics, emphasizing the importance of proactive measures in healthcare planning.

Background: The lifestyle of the Arab population in Israel has changed in the last few decades, and modernization and urbanization have impacted the prevalence of chronic diseases.

Objectives: To investigate the prevalence of chronic diseases in the Arab population compared to the Jewish population in Israel.

Methods: This retrospective study included Arab and Jewish people insured by Israel’s largest health maintenance organization. Demographic data and data regarding chronic diseases were collected. Crude prevalence and age group adjusted prevalence were calculated.

Results: In total, 863,116 Arab and 3,674,863 Jewish people were included in the analysis. We found that 18.3% of the Arab population had a diagnosis of diabetes mellitus and 28.8% had obesity compared to 17.5% and 22.5% in the Jewish population, P < 0.001, respectively. The prevalence of chronic heart failure, chronic ischemic heart disease, cerebrovascular accidents, hypertension, and myocardial infarction among Arabs was higher in all age groups compared to Jewish patients. Arab males had higher frequency rates of obesity and hemodialysis treatment compared to Jewish males. The proportion of women with diabetes mellitus, hemodialysis treatment, iron deficiency anemia, or obesity was greater among Arab females.

Conclusions: Significant differences were found in the prevalence of chronic diseases among Arab and Jewish patients in Israel. Culturally relevant interventions are crucial for disease prevention, early diagnosis, and management of chronic diseases among different ethnic groups.

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.