Israel Medical Association Journal

A review of the literature on the effect of immune modulation on the skeleton shows disappointing results.

Background: Little is known about phenotypical variations among ethnic groups in patients with Parkinson's disease (PD) in Israel. Clinical characteristics of non-Ashkenazi Jews (NAJ) are scantly described.

Objectives: To describe clinical aspects of PD in ethnic groups in Israel, focusing on NAJ and Ashkenazi Jews (AJ).

Methods: In this cross-sectional retrospective study, we collected demographic, genetic, and clinical characteristics of patients from different ethnic Jewish backgrounds. Ethnic groups included AJ; North African Jews (NAFJ); oriental Jews (OJ) originating from Iran, Iraq, and Buchara; Balkan Jews; Yemenite Jews (YJ); and Jews of mixed origin. Clinical characteristics included hyposmia, urinary complaints, constipation, and rapid eye movement sleep behavioral disorder. Cognitive complaints, motor features, levodopa-induced dyskinesia, and motor fluctuations were collected. Motor part of the MDS-UPDRS and Hoehn and Yahr scores were collected.

Results: The study comprised 174 PD Jewish patients (63.2% AJ, 56.4% males). The age at onset was 65.3 ± 10.2 years; 106 patients (60.9%) were genotyped (17 glucocerebrosidase [16.0%], 13 leucine-rich repeat kinase 2 [LRRK2] [12.3%]). Rates of hyposmia were significantly higher in AJ than NAJ (56.6% vs. 39.5%, respectively, P = 0.003). No significant differences were found in motor features in all variables. Of 13 AJ patients carrying the LRRK2 mutation, only one had hyposmia. Three patients with LRRK2 were NAJ.

Conclusions: Hyposmia is less prevalent in PD patients of NAJ origin than in AJ. The rate of hyposmia in NAFJ patients is particularly low. The rate of other non-motor features is similar between NAJ and AJ patients.

Background: Morbidly adherent placentation (MAP) increases the risk for obstetric hemorrhage. Cesarean hysterectomy is the prevalent perioperative approach. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive and relatively simple endovascular procedure to temporarily occlude the aorta and control below diaphragm bleeding in trauma. It has been effectively used to reduce obstetric hemorrhage.

Objectives: To evaluate whether REBOA during cesarean delivery (CD) in women with morbidly adherent placentation is a safe and effective treatment modality.

Methods: We introduced REBOA for CD with antepartum diagnosis of MAP in 2019 and compared these patients (RG) to a standard approach group (SAG) treated in our center over the preceding year, as a control. All relevant data were collected from patient electronic files.

Results: Estimated blood loss and transfusion rates were significantly higher in SAG; 54.5% of SAG patients received four RBC units or more vs. one administered in RG. No fresh frozen plasma, cryoprecipitate, or platelets were administered in RG vs. mean 3.63, 6, and 3.62 units, respectively in SAG. Ten SAG patients (90.9%) underwent hysterectomy vs. 3 RG patients (30%). Five SAG patients (45%) required post-surgical intensive care unit (ICU) admission vs. no RG patients. Bladder injury occurred in five SAG cases (45%) vs. 2 RG (20%). One RG patient had a thromboembolic event. Perioperative lactate levels were significantly higher in SAG patients.

Conclusions: Use of REBOA during CD in women with MAP is safe and effective in preventing massive bleeding, reducing the rate of hysterectomy, and improving patient outcome.

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.

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: Perivascular cuffing as the sole imaging manifestation of pancreatic ductal adenocarcinoma (PDAC) is an under-recognized entity.

Objectives: To present this rare finding and differentiate it from retroperitoneal fibrosis and vasculitis.

Methods: Patients with abdominal vasculature cuffing were retrospectively collected (January 2011 to September 2017). We evaluated vessels involved, wall thickness, length of involvement and extra-vascular manifestations.

Results: Fourteen patients with perivascular cuffing were retrieved: three with celiac and superior mesenteric artery (SMA) perivascular cuffing as the only manifestation of surgically proven PDAC, seven with abdominal vasculitis, and four with retroperitoneal fibrosis. PDAC patients exhibited perivascular cuffing of either or both celiac and SMA (3/3). Vasculitis patients showed aortitis with or without iliac or SMA cuffing (3/7) or cuffing of either or both celiac and SMA (4/7). Retroperitoneal fibrosis involved the aorta (4/4), common iliac (4/4), and renal arteries (2/4). Hydronephrosis was present in 3/4 of retroperitoneal fibrosis patients. PDAC and vasculitis demonstrated reduced wall thickness in comparison to retroperitoneal fibrosis (PDAC: 1.0 ± 0.2 cm, vasculitis: 1.2 ± 0.5 cm, retroperitoneal fibrosis: 2.4 ± 0.4 cm; P = 0.002). There was no significant difference in length of vascular involvement (PDAC: 6.3 ± 2.1 cm, vasculitis: 7.1 ± 2.6 cm, retroperitoneal fibrosis: 8.7 ± 0.5 cm).

Conclusions: Celiac and SMA perivascular cuffing can be the sole finding in PDAC and may be indistinguishable from vasculitis. This entity may differ from retroperitoneal fibrosis as it spares the aorta, iliac, and renal arteries and demonstrates thinner walls and no hydronephrosis.

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: In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age.

Objectives: To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications.

Methods: We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT).

Results: The study included 2494 women who were diagnosed with breast cancer during 2004–2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6–0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4–2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5–3.4) and less likely OCCP (OR 0.4, 95%CI 0.3–0.6) and HRT (OR 0.4, 95%CI 0.3–0.5).

Conclusions: Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.

Background: Group A Streptococcus (GAS), the predominant bacterial pathogen of pharyngitis, is sometimes difficult to distinguish clinically from viral pharyngitis. Despite the high prevalence of viral pharyngitis in children, antibiotic treatment is common.

Objective: To investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with GAS pharyngitis (GAS-P) at a large pediatric community clinic.

Methods: Antibiotic prescription data were collected from October 2016 to March 2017 (pre-intervention period) and from October 2017 to March 2018 (post-intervention period). The intervention was a one-day seminar for primary care pediatricians on the diagnosis and treatment of GAS-P in children according to national guidelines.

Results: The overall prevalence of testing differed between the two time periods. There was a decrease in children who did not undergo any testing (from 68% to 63%), an increase in streptococcal rapid antigen detection testing (28% to 32%), and a slight increase in throat cultures (3% to 4%) (p = 0.02). There was no change in the types of antibiotics prescribed before and after the intervention (p = 0.152).

Conclusions: The ASP resulted in a slight reduction in the percentage of children who did not undergo laboratory testing for GAS-P and a slight reduction in the percentage of children who received antibiotic treatment. The ASP did not reduce the use of broad-spectrum antibiotics and macrolides.

The portraits of mothers of artists are a distinct genre of female portrait art. Whereas most female portraits were commissioned, the mother portraits were the painter's initiative and reflection of sentiments. In several portraits of the mothers of artists, in particular Rembrandt’s paintings, age-related changes are depicted by the masters and their contemporaries. To some extent, they explain the feelings of James Abbott McNeil Whistler, expressed by the color pattern of the title of his mother portrait, Arrangement in Grey and Black No. 1.

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: Abdominal pathology in pregnant patients is a frequent challenge for emergency department physicians. Ultrasound is the imaging modality of choice but is inconclusive in approximately one-third of cases. Magnetic resonance imaging (MRI) is becoming increasingly available, even in acute settings. Multiple studies have defined the sensitivity and specificity of MRI in this population.

Objectives: To evaluate the use of MRI findings in pregnant patients presenting with acute abdominal complaints to the emergency department.

Methods: This retrospective cohort study was conducted at a single institution. Data were collected on pregnant patients who underwent an MRI for acute abdominal complaints between 2010 and 2019 at a university center. Patient demographics, diagnosis at admission, ultrasound and MRI findings, and discharge diagnosis were recorded and evaluated.

Results: In total, 203 pregnant patients underwent an MRI for acute abdominal complaints during the study period. MRI was found without pathology in 138 cases (68%). In 65 cases (32%), the MRI showed findings that could explain the patient's clinical presentation. Patients presenting with long-standing abdominal pain (> 24 hours), fever, leukocytosis, or elevated C-reactive protein values were at a significantly increased risk of having an acute pathology. In 46 patients (22.6%), MRI findings changed the primary diagnosis and management while in 45 patients (22.1%) MRI findings improved characterization of the suspected pathology.

Conclusions: MRI is helpful when clinical and sonographic findings are inconclusive, leading to changes in patient management in more than one-fifth of patients.

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: Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by determining protein level and coagulation activity (FVII:C). FVII:C measurements are expensive and time consuming.

Objectives: To analyze correlations between PT, international normalized ratio (INR), and FVII:C in pediatric patients before otolaryngology surgery and to establish alternative methods for identifying FVII deficiency.

Methods: FVII:C data were collected from 96 patients with normal aPTT and prolonged PT values during preoperative otolaryngology surgery coagulation workup between 2016 and 2020. We compared demographic and clinical parameters using Spearman correlation coefficient and receiver operating characteristic (ROC) curve analysis to determine the accuracy of PT and INR values to predict FVII deficiency.

Results: The median values of PT, INR and FVII:C were 13.5 seconds, 1.14, and 67.5%, respectively. In total, 65 participants (67.7%) displayed normal FVII:C compared to 31 (32.3%) with decreased FVII:C. A statistically significant negative correlation was observed between FVII:C and PT values and between FVII:C and INR. Despite statistically significant ROC of 0.653 for PT (P-value = 0.017, 95% confidence interval [95%CI] 0.529–0.776) and 0.669 for INR (P-value = 0.08, 95%CI 0.551–0.788), we were unable to determine an optimal cutoff point to predict FVII:C deficiency with high sensitivity and high specificity.

Conclusions: We could not identify a PT or INR threshold to best predict clinically relevant FVII:C levels. When PT is abnormal, determining FVII:C protein levels is needed for diagnosing FVII deficiency and considering surgical prophylactic treatment.

Background: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS).

Objectives: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores.

Methods: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted.

Results: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test.

Conclusions: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.