Israel Medical Association Journal

Background: The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population.

Objectives: To analyze the seroprevalence of EBV infection in different population groups in Croatia.

Methods: During a 2 year period (2015–2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity.

Results: The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age < 9 years to 98.3% in 30–39 year olds, and remained stable thereafter (P < 0.001). The IgG seroprevalence differed significantly among groups: 68.1% in children/adolescents and 95.9% in adults; multiple sclerosis (100%), hemodialysis patients (97.7%), heart transplant recipients (93.8%), hematological malignancies (91.2%), and Crohn’s disease (88.5%), P < 0.001. IgM antibodies were detected in 9% of participants. Using IgG avidity, recent primary EBV infection was documented in 83.8% of IgM-positive subjects < 9 years old, 69.2% age 10–19, 33.3% age 20–29, and 3.6–4.2% > 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic regression showed that age is associated with EBV IgG seropositivity.

Conclusions: EBV is widespread in the Croatian population. Older age appears to be the main risk factor for EBV seropositivity.

Background: Physical inactivity is a pivotal factor in the development and progression of various chronic diseases. However, most fitness facilities exclude unhealthy individuals. Therefore, an exercise program that admits such patients is imperative.

Objectives: To evaluate the effectiveness of a fitness facility that admits adult subjects with multiple chronic diseases.

Methods: We conducted a retrospective screening of patient records from the Medical Fitness Facility at Meir Medical Center, Israel. Intake of subjects was done by a multidisciplinary team. For each individual, personalized diet and exercise plans were developed and patients attended the facility twice a week. Each participant was evaluated at enrolment and after 4 months for well-being, metabolic parameters, exercise capacity, and laboratory blood tests.

Results: A total of 838 individuals were enrolled, mean age 57 years. Their medical conditions included dyslipidemia (48.8%), hypertension (37.6%), and diabetes mellitus (24.9%), followed by musculoskeletal problems (arthropathy 19%, lower back pain 16.1%) and ischemic heart disease (13.4%). Less common diagnoses were vascular diseases, pulmonary diseases, and malignancy. Only 40.5% of participants adhered to the regimen with advanced age being the best predictor for adherence. At the follow-up visit, body mass index was lower (31.2 vs. 30.2 kg/m², P <0.0001), exercise capacity increased (measured as maximal MET; 7.1 vs. 8.1, P < 0.0001), and well-being improved (measured by Short Form Survey [SF-36]; 69.3 vs. 76.0, P <0.0001).

Conclusions: We show that a fitness program for patients with multiple chronic diseases is feasible and effective in improving prognostic parameters, albeit significantly challenged by adherence limitations.

Background: Neuroblastoma is the most common non-central nervous system (CNS) solid malignant tumor in children. The surgical treatment of high-risk neuroblastoma presents a challenge, and the benefits of aggressive surgical resection have been called into question.

Objectives: To examine our experience with surgical resection of neuroblastoma.

Methods: We report on a retrospective chart review of our preliminary surgical experience in 25 patients with neuroblastoma who underwent surgery performed by a single surgeon at two institutions over a 3 year period. Demographic data, including stage of tumor and risk stratification, were recorded. Primary outcome was total gross resection. Patients were followed for 3 years after surgery.

Results: We found that 80% of the patients, including those with high-risk neuroblastoma tumors, had total gross resection of their tumor with minimal operative morbidity and no mortality; 88% had greater than 90% resection of their tumor. Overall, 3 year survival was 84% (21/25).

Conclusions: Resection of neuroblastoma, even large, high-risk, bilateral tumors, was possible when performed by surgical teams with considerable experience.

Axial spondyloarthritis (axSpA) covers the stage of non-radiographic axial spondyloarthritis (nr-axSpA) and classic ankylosing spondylitis. The pathognomonic findings of axSpA are mainly inflammatory and osteoproliferative changes in the sacroiliac joints (SIJ) and the spine. Various imaging techniques are being used in daily practice for assessment of disease-specific changes, such as periarticular bone marrow edema, erosions, sclerosis, fat metaplasia and ankylosis in the SIJ or spondylitis, spondylodiscitis, facet joint involvement, or syndesmophytes in the spine of patients with axSpA. Conventional radiographs are still considered the gold standard for assessment of structural changes, while the method of for detection of inflammatory changes is magnetic resonance imaging (MRI).

A result for an MRI in the SIJ is considered positive for axSpA when more than one lesion is present on one MRI slice, If there is one lesion only, this should be present on at least two consecutive slices. For the spine, inflammatory lesions should preferably be located in the corner of the vertebral bodies, while occurrence of spondylitis in three or more vertebral corners is considered highly suggestive of axSpA.

This review gives a detailed overview about the benefits and limitations of all available imaging techniques in patients with axSpA, explains the usage of imaging techniques in the context of diagnosis and differential diagnosis of the disease, and reports on the potential future trends in the area of imaging of the axial skeleton in patients who are suspicious for this diagnosis.

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: Weight loss surgery is the most effective treatment for obesity, and it reduces cardiovascular and cancer risk through poorly understood mechanisms. MicroRNAs (miRNAs) are short RNA molecules that regulate the stability and translation of many mRNAs. We hypothesized that levels of specific circulating miRNAs are altered following surgery and may contribute to lower cancer risk.

Objectives: To investigate the change of miRNA following surgery.

Methods: All patients underwent gastric “sleeve operation”. RNA was isolated from sera of 21 patients (14 men, 7 women) before and 3 months after surgery. Sera were combined into two pools, which served for cDNA library construction followed by miSeq sequencing. The levels of candidate miRNAs were validated in the individual samples by QRT-PCR.

Results: Serum miR-122 was significantly up-regulated 3 months post-bariatric surgery in sera of patients, whose endothelial function had greatly improved. In addition, serum miR-122 levels correlated positively with endothelial function as measured by FMD. The changes in miR-122 levels from pre-surgery to 3 months post-surgery also tended to correlate with the respective changes in FMD.

Conclusions: The serum miR-122/miR-451 ratio may serve as a marker for endothelial function in obese patients. miR-122 is the dominant miRNA in the liver and a known tumor suppressor. Our findings suggest a role for circulating miR-122 in the maintenance of vascular endothelial cells (VECs) and in the prevention of cancer. Further studies are required to elucidate the mechanism of its secretion into circulation and its absorption by VECs, as well as its relevant cellular targets.

Background: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation.

Objectives: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel.

Methods: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study.

Results: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%.

Conclusions: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

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. 

 

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. However, a subgroup of patients experiences extraglandular manifestations which worsens disease prognosis. To date evidence based guidelines for the management of pSS are lacking, hence the therapeutic approach is mainly based on expert opinion and data from other connective tissue diseases. In recent years, several studies have explored the efficacy and safety of biologic agents in pSS and after the failure of tumor necrosis factor inhibitors, the attention has been focused on compounds directly targeting B or T lymphocytes. The aim of this review article is to provide an overview of available data about B and T cell targeting in pSS and of future directions based on ongoing trials. 

Background: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. 

Objective: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). 

Methods: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. 

Results: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. 

Conclusions: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i. 

 

Background: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. 

Objectives: To analyze the interplay between TD and PF in a cohort of SSc women. 

Methods: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. 

Results: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). 

Conclusions: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.