Israel Medical Association Journal

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.

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 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: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Background: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation).

Objectives: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula.

Methods: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded.

Results: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group.

Conclusions: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

Background: Age-related changes in multiparametric magnetic resonance imaging (mpMRI) of the prostate have been reported in the general population but not in screening cohorts.

Objectives: To evaluate age-related changes on prostatic mpMRI in a screening cohort of BRCA1/2 mutation carriers.

Methods: Asymptomatic BRCA1/2 mutation carriers underwent mpMRI as part of a screening program. All included patients were followed for 3 years with no evidence of prostate cancer. mpMRIs were retrospectively evaluated by two abdominal radiologists for peripheral zone (PZ) patterns on T2 (homogenous hyperintensity, wedge-shaped hypointensities, patchy hypointensities, or diffuse hypointensity), and transition zone (TZ) pattern on T2 (homogenous, heterogeneous, nodular). Apparent diffusion coefficient (ADC) values of PZ and TZ were measured. Statistical analysis was performed using a predefined age cutoff of 50 years old.

Results: Overall, 92 patients were included: 38 in the younger age group (40–49 years) and 54 in the older age group (50–69 years). PZ homogenous hyperintensity and wedge-shaped hypointensities were more common in the older patients, whereas diffuse hypointensity was more common in younger patients (P < 0.001 for both readers) with substantial inter-reader agreement between the readers (kappa=0.643). ADC values were lower in young patients in the PZ (P < 0.001) and TZ (P = 0.003).

Conclusions: Age-related differences in mpMRI were validated in BRCA mutation carriers. As some features overlap with prostatic carcinoma, awareness is crucial, specifically to diffuse T2 hypointensities of the PZ and lower ADC values in the PZ and TZ, which are more common in younger patients.

Background: Brucellosis is an endemic infection affecting the Mediterranean Basin, Arabian Peninsula, India, Mexico, and South America. Data on brucellosis infections in children are limited.

Objectives: To review and characterize the clinical presentation of pediatric patients diagnosed with brucellosis in a tertiary medical center.

Methods: Retrospective data analysis was conducted on all pediatric patients from January 2010 to December 2020 admitted to the pediatric department with a diagnosis of brucellosis based on a positive serology test or growth of Brucella bacteria in blood culture.

Results: The study comprised 53 children aged 0–18 years. The mean age at presentation was 11.01 ± 4.91 years; 39 male (73.6%). Pre-infection exposure to unpasteurized milk or unvaccinated livestock was reported in 37 (69.8%). Fever was present in 64.6%, followed by arthralgia (49%), loss of appetite (42.3%), and weight loss (24.6%). Gastrointestinal symptoms were reported in 52.8% and included abdominal pain (34.6%), nausea (28.3%), vomiting (24.5%), and diarrhea (2.6%). Eight patients experienced pancytopenia (15.1%). The median length of intravenous antibiotic treatment was 7 days (range 3–14 days) and for oral antibiotic treatment 6 weeks (range 2–24 weeks). Most patients were initially treated with intravenous gentamycin (90.5%) and long-term oral antibiotics, most commonly doxycycline. Two (3.7%) required admission to the pediatric intensive care unit. No mortality was documented, and all cases of relapses were successfully treated.

Conclusions: Pediatric brucellosis is an acute febrile disease often associated with rheumatologic complaints. Patients 8–18 years of age also presented with headache, weight loss, and night sweats.

Background: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases.

Objectives: To investigate the association between dementia and PM/DM.

Methods: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort.

Results: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77–1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57–2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67–17.67, P = 0.005).

Conclusions: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.

Background: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained.

Objectives: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study.

Methods: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI).

Results: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7–9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001).

Conclusions: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Background: Infants younger than 6 months of age are not eligible for coronavirus disease 2019 (COVID-19) vaccinations. Maternal variables during pregnancy and the postnatal period may affect the clinical and laboratory course of COVID-19 positive infants.

Objective: To assess the clinical manifestation and laboratory differences in infants with three maternal variables: breastfeeding, vaccinated, and co-illness.

Methods: We conducted a single-center retrospective cohort study of positive COVID-19 infants with three subgroups of maternal variables. The population included infants under 6 months of age hospitalized due to COVID-19. Data about clinical features, laboratory tests, and maternal information including vaccination status, breastfeeding status and maternal positive COVID-19 infection was gathered. All variables were compared among the three subgroups.

Results: Breastfed infants had shorter hospitalization period (mean 2.61 ± 1.378 days) compared to non-breastfed infants (mean 3.8 ± 1.549) (P = 0.051). COVID-19 infants of positive COVID-19 mothers had a higher absolute neutrophil count (mean 4.4 ± 3.8) compared to infants of COVID-19 negative mothers (mean 2.7 ± 2.4) (P = 0.042).

Conclusion: Breastfeeding was associated with shorter periods of hospitalization in COVID-19 positive infants. In addition, positive COVID-19 infants of mothers who were positive for COVID-19 are likely to have a higher absolute neutrophils count.

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances.

Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet.

Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups.

Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04).

Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Background: Uterine tachysystole during labor can lead to a decrease in fetal oxygen saturation and intracerebral oxygen saturation. Acute tocolysis using atosiban can inhibit uterine smooth muscle activity, potentially improving fetal status and facilitating vaginal delivery or allowing time to prepare for operative delivery.

Objectives: To compare maternal and neonatal outcomes in cesarean and vaginal deliveries following atosiban administration during fetal prolonged deceleration and tachysystole at gestational age 37 0/7 to 43 0/7 weeks.

Methods: We conducted a single-center, descriptive retrospective cohort study at a large tertiary referral center.

Results: Of the 275 patients treated with atosiban, 186 (68%) delivered vaginally (either spontaneous delivery or instrumental delivery) and 89 (32%) underwent a cesarean delivery. In a univariate analysis, cesarean delivery was associated with higher body mass index (27.9 ± 4.3 vs. 30.2 ± 4.8, P = 0.003). Second stage atosiban administration was associated with vaginal delivery (89.3% vs. 10.7%, P = 0.01). Cesarean delivery was associated with lower Apgar at 1 and 5 minutes and a higher rate of neonatal intensive care unit admissions. The incidence of PPH among women treated with atosiban in our study (2.3–4.3%) was higher than the incidence reported in the literature (1–3%)  

Conclusions: Atosiban may be an effective acute intervention for non-reassuring fetal heart rate during tachysystole, increasing the rate of vaginal delivery and potentially reducing the need for cesarean delivery. However, the potential risk of postpartum hemorrhage should be taken into consideration.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.