Israel Medical Association Journal

Background: Acquired hepatocerebral degeneration (AHD) is a neurologic complication of severe chronic liver disease (CLD) with portosystemic shunts. The proposed etiology is manganese accumulation in the brain tissue, especially in the basal ganglia. Combination of clinical manifestation, mostly extrapyramidal movement disorders, and hyperintensities on T1-weighted brain magnetic resonance imaging (MRI) is diagnostic. Although liver transplantation controversial, it is suggested for AHD.

Objectives: To depict clinical and neuroimaging characteristics and response to treatments in patients diagnosed with AHD at Sheba Medical Center.

Methods: Review of patients with AHD diagnosis at the Liver Diseases Center at Sheba Medical Center between 2012 and 2017, data of clinical and neuroimaging, follow-up, and response to treatments, including liver transplantation were recorded.

Results: Five patients with diagnosis of AHD were identified, median age at diagnosis 55 years (range 45–64 years). Four patients had cirrhosis at the time of AHD diagnosis. The main risk factor for AHD was the presence of portosystemic shunts. The most prevalent clinical manifestations were movement disorders, specifically a combination of extrapyramidal and cerebellar signs including instability, rigidity, tremor, bradykinesia, and cognitive impairment. Brain MRI revealed hyperintensities on T1-weighted images in the basal ganglia in all patients. Administration of antiparkinsonian drugs showed clinical improvement, whereas liver transplantation performed in two patients was not associated to neurological improvement.

Conclusions: AHD is related to portosystemic shunts. The combination of Parkinsonism and cerebellar signs and MRI pallidal lesions should alert physicians to the diagnosis. The role of liver transplantation in AHD is still controversial.

Background: Low back pain has been the leading cause for disability worldwide for several decades, and clinical guidelines for its management clearly emphasize a multifactorial approach. Yet, current guidelines are still not well implemented by clinicians.

Objectives: To explore the attitudes of family medicine residents regarding low back pain and to determine whether they positively correlate with their treatment approaches. To test if these attitudes can be affected by the Enhanced Transtheoretical Model Intervention (ETMI), a guideline-based workshop.

Methods: Participants completed an online questionnaire regarding their attitudes toward low back pain and clinical habits, after which they attended an online ETMI educational workshop. One month later all participants were asked to complete the questionnaire a second time. Statistical analysis was conducted to explore the attitudes of the residents and clinical approaches, as well as any associations between them, as well as possible differences pre- and post-intervention.

Results: The participants exhibited highly psychologically oriented attitudes. Correlations between the attitudes and treatment did not show consistent coherency. Results regarding the participants clinical approaches were revealed to have two distinct and opposed inclinations: biomedically and biopsychosocially. Last, results for the re-activation subscale were significantly higher post-intervention.

Conclusions: Family medicine residents seem to be highly psychologically oriented regarding low back pain; however, they do not necessarily treat their patients accordingly. Their clinical choices seem to follow two different approaches: guideline-consistent and non-guideline-consistent. An ETMI guideline-based workshop may sway their attitudes toward re-activation of patients. Further research is needed to determine whether similar results would arise in larger physician populations.

Background: Evaluation of children's anthropometrics poses challenges due to age-related changes. The main focus is on height and weight. However, since weight is height-dependent, body mass index (BMI) is the best surrogate measurement of adiposity. Israel has not developed national growth tables; therefore, researchers and clinicians utilize either World Health Organization (WHO) or U.S. Centers for Disease Control and Prevention (CDC) tables as benchmarks.

Objectives: To evaluate the anthropometrics of Israeli children benchmarked by CDC and WHO tables.

Methods: A retrospective review was conducted of the 1987–2003 birth cohort (age 4–18 years) from Clalit Health Services databases. Anthropometrics were retrieved twice: at study entry and one year later. We evaluated them as separate cohorts. Gender-specific age-matched median height and BMI were compared with CDC and WHO height and BMI tables.

Results: The study consisted of 15,650, mean age at study entry 9.5 years (range 4–18). Gender-specific median heights of the Israeli children were similar to CDC and WHO values at younger ages, but were slightly shorter than the age-matched CDC and WHO toward the age of final height in both cohorts. However, gender-specific median BMI was considerably and statistically significant higher compared to CDC and WHO values consistently along the entire age range in both cohorts.

Conclusions: Israeli children were slightly shorter toward the age of final height, compared to WHO and CDC. However, BMI in Israeli children was significantly higher compared to the CDC and WHO consistently along the age range, which raises an alarm regarding obesity patterns

Background: The number of patients undergoing shoulder arthroplasty is increasing yearly.

Objectives: To evaluate the results of a consecutive series of patients who underwent shoulder replacement for a variety of indications in a single medical center in Israel.

Methods: All shoulder arthroplasties performed in our institution between 2006 and 2015 were retrospectively reviewed. The functional outcomes and satisfaction of 180 shoulder arthroplasties were evaluated for objective and subjective parameters using the American Shoulder and Elbow Surgeons Shoulder Score (ASES), the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure, and the Short Form Health Survey (SF-12).

Results: The indications for surgery were osteoarthritis (n=35), rotator cuff arthropathy (n=32), fractures (n=99), and other reasons (n=14). The mean follow-up was 52 months. The scores improved markedly among the patients who underwent surgery later in the study period. The mean DASH score before 2012 was 48.8 and improved to 37.2 after 2013. The respective ASES also improved from 54.2 to 68.6. The use of hemiarthroplasty decreased from 85% to 33% as of 2013, while the use of total shoulder arthroplasty increased.

Conclusions: Shoulder arthroplasty represents an effective treatment modality with satisfactory functional outcomes. Our current study demonstrates a shift from hemiarthroplasty to total shoulder arthroplasty, with the number of procedures increasing yearly. Surgeon experience and the expanding volume of operations had a direct positive effect on the functional outcomes of shoulder arthroplasties.

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy).

Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery.

Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan–Meier method.

Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50–62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52–87%), LC was 84% (95%CI 65–93), and DFS 35% (95%CI 14–59). Grade 4–5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01).

Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Background: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. 

Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. 

Methods: In March 2013 the authors launched a seven-component intervention program: 

1. Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory


2. Education program for the emergency department staff


3. Dissemination of information regarding the urgency of the PPCI decision


4. Activation of the catheterization team by a single phone call


5. Reimbursement for transportation costs to on-call staff who use their own cars


6. Improvement in the quality of medical records


7. Investigation of failed cases and feedback 

Results: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. 

Conclusions: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival. 

 

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

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: The popularity of bicycle riding for recreation, exercise and transportation has grown enormously in recent years, which has led to an increased incidence of bicycle-related injuries. While these injuries involve mainly the musculoskeletal system, data on shoulder-specific injuries incurred while bike riding are lacking. Classifying these shoulder injuries may provide insight and assistance in the creation and implementation of effective protective gear and measures. 

Objectives: To investigate the types and mechanisms of shoulder injuries among cyclists.

Methods: This study retrospectively examined all cyclists who incurred shoulder injuries while riding and were admitted to the emergency department and shoulder clinic between January 2008 and November 2013. The study included 157 subjects with various bicycle-related shoulder injuries treated with either conservative or surgical measures. 

Results: Eighty-four percent of injuries were caused by a direct blow to the shoulder, 7% by falling on an outstretched hand, 6% were traction injuries, and 3% were due to hyper-abduction. Nine different clinical types of injury were observed; the most common injuries were clavicle fractures (32%), followed by acromioclavicular joint dislocations (22%), rotator cuff tears (22%), and humeral fractures (8%). Fifty-one percent of subjects were managed with conservative care and the remaining patients required surgical interventions. 

Conclusions: The shoulder injuries incurred while riding a bicycle span the entire spectrum of shoulder injuries and often result in debilitating conditions. Although the use of helmets is increasing, there is currently no effective protective gear or measures to prevent riders from suffering shoulder injuries. 

 

Background: Atypical presentation of tuberculosis (TB) during pregnancy may cause diagnostic delay and adversely influence pregnancy outcome. 

Objectives: To examine the incidence and clinical and epidemiological features of TB during pregnancy and investigate infection control measures at delivery and during the postpartum period.

Methods: We retrospectively evaluated all reported cases of TB diagnosed during pregnancy to 6 months postpartum in Israel’s Northern Health District (2002–2012). 

Results: Active TB was detected in six patients; all were negative for human immunodeficiency virus (HIV). Two patients were diagnosed in the postpartum period, and four had pulmonary involvement. The average incidence during this period (3.9 per 100,000 pregnancies) was similar to that in the general population. Five patients were at high risk of contracting TB due to either recent immigration from a high-burden country or being in contact with another individual with active TB. Patients with pleuropulmonary involvement had prolonged cough and abnormal chest X-rays, without fever. Diagnosis was delayed for 3 to 7 months from symptom onset. Investigation of the newborn to rule out intrauterine infection was conducted in only one of four relevant cases. All patients were infected with organisms susceptible to all first-line drugs, and all were cured with standard therapy.

Conclusions: There was a considerable delay in the diagnosis of TB among pregnant women, and investigation of the newborn upon delivery to rule out TB infection was routinely omitted. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including an obstetrician, pediatrician, TB specialist, and public health physician.

 

Objectives: To retrospectively determine the clinical response to ¹³¹I-MIBG therapy at low doses in patients with refractory neuroblastoma.

Methods: We performed a retrospective chart review of 10 patients with neuroblastoma treated with ¹³¹I-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of ¹³¹I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course.

Results: Twenty-one courses of ¹³¹I-MIBG were delivered to 10 patients (3 girls, 7 boys). Their mean age was 3.8 years (range 1.5–6 years). All patients received several protocols of chemotherapy including the high dose form. Three patients received three courses of ¹³¹I-MIBG with a minimum of 6 weeks between each course, five patients received two courses, and two patients received only one course. An objective response to the first course was obtained in nine patients and to the second course in six of eight, and in three children who underwent the third course the pain decreased. One patient has no evidence of disease, four are alive with disease, and five died of the disease. No unanticipated toxicities were observed.

Conclusions: Low dose ¹³¹I-MIBG is an effective and relatively non-toxic treatment in neuroblastoma disease palliation. Rapid and reproducible pain relief with ¹³¹I-MIBG was obtained in most of the children. Treatment with systemic radiotherapy in the form of low dose ¹³¹I-MIBG was easy to perform and effective in cases of disseminated neuroblastoma, demonstrating that this primary therapy can be used for palliative purposes.

Background: Acute, as opposed to chronic, anterior uveitis is rarely associated with macular or optic nerve  edema. Nevertheless, mild changes may not be visible on examination.

Objectives: To implement non-invasive ocular coherence tomography (OCT) for obtaining quantitative and qualitative data in the assessment of changes in macular morphology and peripapillary retinal nerve fiber layers in eyes with acute anterior uveitis.

Methods: This retrospective case-control study was conducted in patients with unilateral acute anterior uveitis lasting for up to one month. Patients with evidence of other ocular disease or who had undergone intraocular surgery were excluded. We reviewed the charts of 14 consecutive patients who were diagnosed with acute unilateral anterior uveitis between 2007 and 2008 at the Tel Aviv Medical Center. Data on demographic details, ophthalmic examination, macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness (as demonstrated by OCT) were retrieved. Retinal and RNFL thickness was compared between the healthy fellow eye (control) and the uveitic eye in the central and four perifoveal quadrant regions, and RNFL thickness was compared in the mean and four quadrant values by Student’s t-test.

Results: We evaluated 28 eyes of 7 males and 7 females (mean age 37.7 years, range 20–65). The diagnoses were: idiopathic in five patients, ankylosing spondylitis in five, Crohn’s disease in one patient and reactive arthritis in one. Nine patients were HLA-B27 positive. The retina and the peripapillary NFL in each area were thicker in the uveitic eyes compared to the controls. The difference was statistically significant. There was no correlation between the differences in OCT values and patients’ demographic characteristics.

Conclusions: OCT demonstrated that eyes with acute anterior uveitis had thicker maculae and thicker peripapillary RNFL than controls. This finding suggests that even milder anterior uveitis may be associated with some degree of posterior segment manifestations.

Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin®) and ranibizumab (Lucentis®) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.

Objectives: To describe the current application of anti-VEGF[1] drugs among retinal specialists in Israel.

Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.

Results: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient’s socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series if the first one yielded no improvement in fluid status. The routine practice for intravitreal injection (> 80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.

Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies.