Israel Medical Association Journal

Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS.

We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diagnosis the patient received prenatal counseling and benefited from the optimal treatment of Obs-APS that led to a successful pregnancy. The applicability of this successful experience about outcomes in women with non-criteria, or seronegative, Obs-APS is also evaluated.

 

Background: In recent years cardioversion of atrial fibrillation has become a routine procedure, enabling symptomatic functional improvement in most cases. However, some patients develop complications after cardioversion. Identifying these individuals is an important step toward improving patient outcome.

Objectives: To characterize those patients who may not benefit from cardioversion or who may develop complications following cardioversion.

Methods: We retrospectively analyzed 186 episodes of cardioversion in 163 patients with atrial fibrillation who were admitted to our cardiology department between 2008 and 2013 based on their clinical and echocardiographic data. Patients were divided into two groups: those with uncomplicated cardioversion, and those who developed complications after cardioversion.

Results: Of the 186 episodes, cardioversion was done in 112 men (60%) and 74 women (40%), P < 0.00001. Complications after cardioversion occurred in 25 patients (13%). These patients were generally older (72 vs. 65 years, P < 0.01), were more often diabetic (52% vs. 27%, P = 0.005), had undergone emergency cardioversion (64% vs. 40%, P = 0.01), had left ventricular hypertrophy (left ventricular mass 260 vs. 218 g, P = 0.01), had larger left atrium (left atrial volume 128 vs. 102 ml, P < 0.009), and more often died from complications of cardioversion (48% vs. 16%). They had significant mitral regurgitation (20% vs. 4%, P = 0.03) and higher pulmonary artery pressure (50 vs. 42 mm Hg, P < 0.02).

Conclusions: People with complications after cardioversion tend to be older, are more often diabetic and more often have severe mitral regurgitation. In these patients, the decision to perform cardioversion should consider the possibility of complications.

Background: Atrial fibrillation (AF) is the most common arrhythmia and a common cause of ischemic stroke. Stroke patients with AF have been shown to have a poorer neurological outcome than stroke patients without AF.

Objectives: To determine the impact of pre-existing AF on residual degree of disability in patients treated with IV thrombolysis.

Methods: In this case-control study, data of 214 stroke patients (63 with AF and 151 without AF) were collected from the National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database. Stroke severity and outcome were compared using the National Institute of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on admission and discharge. Demographics and stroke characteristics were also compared between the groups.

Results: Stroke severity, as determined by NIHSS at admission, was higher in the AF group than the non-AF. In the group of patients who were treated with intravenous tissue plasminogen activator (tPA), more patients had favorable outcomes (mRS = 0–1 on discharge) in the non-AF group than in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to 5.05).

Conclusions: Our study suggests worse outcome in thrombolized patients with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor prognostic factor for tPA sensitivity regarding the chance of revascularization and recovery after intravenous tPA.

Background: Accurate assessment of liver fibrosis is crucial for the management of patients with hepatitis C virus (HCV) infection.

Objectives: To evaluate the performance of liver segment-to-spleen volume ratio in predicting the severity of liver fibrosis.

Methods: Sixty-four consecutive HCV patients were enrolled in this retrospective study. All patients underwent contrast-enhanced computed tomography (CT) and were divided into three groups based on their hepatic fibrosis stage evaluated by shear-wave elastography (SWE): non-advanced (F0–F1, n=29), advanced (F2, n=19) and severe fibrosis (F3–F4, n=16). Using semi-automated liver segmentation software, we calculated the following liver segments and spleen volumes for each participant: total liver volume (TLV), caudate lobe (CV), left lateral segment (LLV), left medial segment (LMV), right lobe (RV) and spleen (SV), a well as their ratios: CV/SV, RV/SV, LLV/SV, LMV/SV and TLV/SV.

Results: RV/SV was found to discriminate between patients with non-advanced and advanced fibrosis (P = 0.001), whereas SV, CV, RV, TLV/SV, LMV/SV and RV/SV discriminated between patients with advanced and severe fibrosis (P < 0.05). RV/SV ≤ 3.6 and RV ≤ 2.9 were identified as the best cutoff values to differentiate non-advanced from advanced fibrosis and advanced from severe fibrosis with sensitivities of 72.2% and 92.7%, specificities of 72.7% and 77.8%, and with an area under the receiver operating characteristic (ROC) curve of 0.797 and 0.847, respectively (P ≤ 0.002).

Conclusions: RV/SV may be used for the assessment and monitoring of liver fibrosis in HCV patients prior to the administration of antiviral therapy, considering SWE as the reference method.

Background: Cannabidiol (CBD)-based treatments for several diseases, including Tourette’s

syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be beneficial and the  scientific clinical background of the drug is continuously evolving. 

Objectives: To investigate the short-term effect of CBD-enriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine. 

Methods: In this anecdotal, retrospective, “compassionate-use”, observational, open-label study, 12 females (age 12–24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2–5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients’ quality of life was evaluated using the medical outcome short-form health survey questionnaire (SF-36).

Results: Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. SF-36 showed significant benefits in the physical component score (P < 0.02), vitality (P < 0.03) and social role functioning (P < 0.02) after the treatment. The administration of hemp oil also significantly reduced body pain according to the SF-36 assessment. No significant differences from the start of treatment to several months post-treatment were detected in role limitations due to emotional reactions (P = 0.02).

Conclusions: This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint. Randomized controlled trials are warranted to characterize the safety profile and efficacy of this compound.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2.

Objectives: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic.

Methods: A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza.

Results: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010–2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010–11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups.

Conclusions: The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.

 

Background: Reference ranges for adult peripheral blood lymphocyte subsets have been established in a few countries. To the best of our knowledge no broad lymphocyte subset analysis of the Israeli population has been reported. 

Objectives: To establish reference ranges for healthy adults in Israel and to describe age- and gender-specific differences, if present.

Methods: Lymphocyte subsets CD3, CD3/CD4, CD3/CD8, CD3-/CD16+/CD56+, CD3/TCRαβ, CD3/TCRγδ, and CD19 were examined by flow cytometry in 326 subjects. Samples were subdivided according to age and gender.

Results: Women of all ages had a significantly higher percentage and absolute counts of CD3/CD4 cells than their male counterparts. Higher CD3/CD4 cells were observed also in the older population (> 50 years). CD3/CD8 and CD3-/CD16+/CD56+ were higher in males. Older males had a lower total lymphocyte percentage and CD19 cells compared to younger men. No significant gender-related differences were observed in percent and number of CD19, CD3/TCRαβ or CD3/TCRγδ at all ages.

Conclusions: These reference values could be useful in further studies for assessing changes that occur in different populations in human pathology.

 

Background: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC.

Objectives: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome.

Methods: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. 

Results: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. 

Conclusions: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

 

Mechanical thrombectomy with stent retrievers is now the reference therapy for acute ischemic stroke (AIS) in the anterior circulation in association with thrombolysis. We conducted an extensive systematic review and meta-analysis to evaluate the clinical and angiographic outcomes of stent-retriever thrombectomy in patients with acute anterior circulation stroke. Available literature published to date on observational studies and three randomized trials (MR CLEAN, ESCAPE, and EXTEND-IA) involving the stent-retriever device were reviewed. Successful recanalization and favorable clinical outcome were defined by a TICI ≥ 2b and modified Rankin Scale score of ≤ 2 at 90 days following AIS, respectively. A total of 2067 patients harboring an anterior circulation stroke were treated with a stent retriever: 433 patients from 3 randomized trials involving the device and 1634 patients from observational studies. Mean NIH Stroke Scale score on admission was 16.6, and mean time from onset to recanalization was 300 minutes. Successful recanalization was achieved in 82% (95%CI 77–86, 31 studies). The 90 day favorable outcome was achieved in 47% (95%CI 42–5.2, 34 studies) with an overall mortality rate of 17% (95%CI 13–20, 31 studies). Symptomatic intracerebral hemorrhage was identified in 6% (95%CI 4–8, 32 studies). In patients with AIS caused by a proximal intracranial occlusion of the anterior circulation, stent-retriever thrombectomy is safe and restores brain reperfusion in four of five treated patients, allowing favorable clinical outcome in one of two AIS patients with large vessel occlusion. 

Background: Only a minority of patients with essential tremor (ET) and Parkinson’s disease (PD) undergo deep brain stimulation (DBS) surgery. Data on patient selection factors are useful.

Objectives: To compare the clinical characteristics of ET and PD patients who underwent DBS surgery with those of patients who had not undergone surgery.

Methods: We abstracted data from the electronic medical records of 121 PD and 34 ET patients who underwent DBS surgery at Columbia University Medical Center during the period 2009–2014. We compared this group with 100 randomly selected PD and 100 randomly selected ET patients at the Center who had not undergone DBS surgery. 

Results: Among other differences, age of onset in PD patients who had undergone surgery was younger than in those who did not: 14.9% vs. 3.0% with onset before age 40 (P = 0.003). They had also tried nearly double the number of medications (3.9 ± 1.7 vs. 2.3 ± 1.5, P < 0.001). Interestingly, there was no difference in the proportion of patients with tremor (81.0% vs. 88.0%, P = 0.16). Medical co-morbidities (heart and lungs) were less common in the PD patients who underwent DBS surgery. In the ET group, tremor causing impairment in activities of daily living occurred in all surgical patients compared to 73.0% of non-surgical patients (P < 0.001). The former had tried nearly double the number of medications compared to the latter (3.2 ± 1.7 vs. 1.3 ± 1.3, P < 0.001).

Conclusions: These data add to our understanding of the numerous clinical factors associated with patient referral to DBS surgery. 

 

Background: Despite the increased worldwide recognition of attention deficit/hyperactivity disorder (ADHD), there is a variability in the diagnostic rate of both ADHD and its co-morbidities. These diversities are probably related to the methodology and instruments used for the diagnosis of ADHD and to awareness and cultural interpretation of its existence. 

Objectives: To identify consistent differences in the clinical profile of Arab and Jewish children with ADHD in Israel who differ in their cultural, ethnic and socioeconomic background. 

Methods: We analyzed the data of 823 children and adolescents with ADHD (516 Jews and 307 Arabs) and compared the clinical characteristics between these two ethnic groups. All patients were evaluated in two neuropediatric and child development centers in northern Israel: one in Haifa and one in Hadera. Children with autism and intellectual disabilities were excluded. 

Results: The distribution of ADHD subtypes was similar in both populations. However, learning disorders and psychiatric co-morbidities (behavioral difficulties and anxiety) were reported more frequently in the Jewish population. The most commonly reported adverse effects to psychostimulants were mood changes, anorexia, headache, insomnia and rebound effect, and were more frequently reported in the Jewish population (42.0% vs.18.0%, P < 0.05).

Conclusions: We assume that these differences are related to cultural and socioeconomic factors. We suggest that the physician take cultural background into consideration when treating patients with ADHD.