Israel Medical Association Journal

Background: Although fat grafting is a common technique to repair defects after breast cancer reconstruction surgery and has a low complication rate, the relation between fat grafting and the risk of breast cancer is unknown. Clinical trials to investigate this connection can elucidate the benefits and potential risks of fat grafting in oncology patients.

Objectives:To establish an efficient experimental model, using magnetic resonance imaging (MRI) scans, for comparing different breast tumor study groups post-fat grafting. 

Methods: Breast tumor cells were injected into immunocompromised mice. After tumors formed they were removed. Liposuction was performed in a female human donor and fat was collected. Cells were extracted from the fat by enzymatic digestion. Immunocompromised mice were randomized into four groups: a preliminary experiment group and three equal groups according to the type of fat graft: (i) fresh fat enriched with adipose-derived mesenchymal stem cells (AdMSCs), (ii) fresh fat without cell enrichment, and (iii) no fat injected. Tumor volume was assessed by serial MRI scans. 

Results: The rate of tumor growth was higher in the enriched fat group compared to the non-enriched fat group. 

Conclusions: This experimental model is an effective measurable method, allowing future investigation of the effect of autologous fat on breast cancer.

 

Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients affected by rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and new intriguing pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration and organ response.

There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors.

Sarcoidosis is a chronic multisystem disease with variable course resulting from the interaction between environmental factors and the immune system of individuals genetically predisposed. The evidence linking sarcoidosis with environmental triggers such as metals is increasing. We describe the case of a 44 year old female with a history of smoking since age 30 and previous mercury dental filling who presented at physical examination with numerous subcutaneous nodules. Laboratory data showed accelerated erythrocyte sedimentation rate and high titer of anti-U1 ribonucleoprotein antibodies (U1-RNP). Skin biopsy and chest X-ray suggested the diagnosis of sarcoidosis. In this report we illustrate the different causes involved in the onset of sarcoidosis.

The increasing use of computerized medical records has made the clinical data of the entire population available for epidemiological research. The resultant accessibility to this information mandates careful adaptions of ethical guidelines regarding the handling of clinical data. At the same time it grants a unique opportunity to explore the clinical nature of health and disease in large populations across all of society’s strata, socioeconomic levels, ethnicities, and geographic locations regardless of their vicinity or distance to tertiary care centers. Analysis of large databases allows us to learn the public‘s behavior towards medical services and to investigate how medical interventions affect outcomes over time. Moreover, interaction between different co-morbidities can also be better understood by large population studies. The huge numbers of patients involved in these studies provide a good model of multivariate analysis, a statistical tool that by following proper population adjustments underlines the true independent associations between different conditions. Nevertheless, the limitations of these studies should be borne in mind, such as in-built imprecision of diagnoses, incompleteness of the medical data, and the fact that these databases were initially planned for clinical and not investigational use. 

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected, and includes corticosteroids, azathioprine, interferon, cyclophosphamide, methotrexate or tumor necrosis factor-alpha and interleukin-1 blockers. We present a case series of four refractory BD patients successfully treated with intravenous immunoglobulins (IVIG). All patients fulfilled International Study Group criteria. The patients’ mean age was 38.75 ± 12.09 years and mean disease duration 10.25 ± 8.5 years. Human leukocyte antigen B51 was positive in two of four patients. In addition to oral aphthosis, all patients suffered from genital ulcers and cutaneous BD-related manifestations; central nervous system involvement and arthralgia were found in two patients. Peripheral nervous system, gastrointestinal and eye involvement occurred in 25% of cases. In all patients, previously treated according to EULAR recommendations without reaching satisfactory results, IVIG induced immediate and sustained response over time without incurring any side effects. We propose IVIG administration as an additional effective and safe treatment option in patients with severe and resistant BD.

Background: Recent studies show that vaccination of health care workers (HCW) might reduce influenza transmission and mortality among hospitalized patients. No studies have compared the incidence of laboratory-proven influenza in vaccinated versus unvaccinated hospital HCW. 

Objectives: To evaluate the effectiveness of influenza vaccination among hospital HCW and to examine the attitudes of this population towards influenza vaccination.

Methods: We performed a prospective cohort study between 1 January and 30 April 2014 of 1641 HCW at our medical center; 733 were vaccinated and 908 not vaccinated. A random sample of 199 subjects was obtained: 97 vaccinated and 102 non-vaccinated. Participating individuals were contacted on a weekly basis during the flu season and were asked to report any respiratory or flu symptoms and, if positive, to undergo a polymerase chain reaction (PCR) test for influenza. 

Results: In the general HCW population, vaccination was more frequent among physicians 298/498 (58%) than among nurses (324/862 (38%) and among males than females. Flu symptoms were reported by 20 of 199 participants, 13 in the non-vaccinated group (12.7%) and 7 in the vaccinated group (7.2%). A positive PCR test for influenza A virus was present in 4 of 20 people tested (20%). All positive cases were from the non-vaccinated group (P = 0.0953). 

Conclusions: Non-vaccinated HCW showed a higher, although not statistically significant, tendency for contracting laboratory-proven influenza than the vaccinated population. The main reasons for vaccination and non-vaccination were personal beliefs and habits. Education efforts are needed to improve compliance. Larger studies could further clarify this issue.

 

Background: Transvenous lead extraction can lead to tricuspid valve damage. 

Objectives: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction.

Methods: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR.

Results: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8–93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%).

Conclusions: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined. 

 

Background: Selection of appropriate reference charts for fetal biometry is mandatory to ensure an accurate diagnosis. Most hospitals and clinics in Israel use growth curves from the United States. Charts developed in different populations do not perform well in the Israeli population.

Objectives: To construct new reference charts for fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), using a large sample of fetuses examined at 14–42 weeks gestational age in a medical center and a community ultrasound unit located in two different regions of Israel. 

Methods: Data from the medical center and the community clinic were pooled. The mean and standard error of each measure for each week was calculated. Based on these, reference charts were calculated using quantiles of the normal distribution. The performance of the reference charts was assessed by comparing the new values to empirical quantiles.

Results: Biometric measurements were obtained for 79,328 fetuses. Growth charts were established based on these measurements. The overall performance of the curves was very good, with only a few exceptions among the higher quantiles in the third trimester in the medical center subsample.

Conclusions: We present new local reference charts for fetal biometry, derived from a large and minimally selected Israeli population. We suggest using these new charts in routine daily obstetric practice.

 

Background: It has been suggested that sleep disordered breathing (SDB) during pregnancy may adversely influence maternal as well as fetal well being.

Objectives: To examine the effect of maternal SDB on neonatal neurological examination and perinatal complications.

Methods: Pregnant women of singleton uncomplicated pregnancies were prospectively recruited from a community and hospital low risk obstetric surveillance. All participants completed a sleep questionnaire in the second trimester and underwent ambulatory sleep evaluation (WatchPAT, Itamar Medical, Caesarea, Israel). They were categorized as SDB (apnea hypopnea index > 5) and non-SDB. Maternal and newborn records were reviewed and a neonatal neurologic examination was conducted during the first 48 hours. 

Results: The study group included 44 women and full-term infants; 11 of the women (25%) had SDB. Mean maternal age of the SDB and non-SDB groups was 32.3 ± 2.8 and 32.5 ± 4.7 years, respectively (P = 0.86). Mean body mass index before the pregnancy in the SDB and non-SDB groups was 25.8 ± 4.7 and 22.0 ± 2.5 kg/m2, respectively (P = 0.028). No differences were found between infants born to mothers with SDB and non-SDB in birth weight (3353.8 ± 284.8 vs. 3379.1 ± 492.4 g), gestational age (39.5 ± 0.9 vs. 39.2 ± 1.5 weeks), 5 minute Apgar scores (9.8 ± 0.6 vs. 9.9 ± 0.3), and neurologic examination scores (95.2 ± 3.9 vs. 94.6 ± 4.1). P value for all was not significant. 

Conclusions: Our preliminary results suggest that maternal mild SDB during pregnancy has no adverse effect on neonatal neurologic examination or on perinatal complications.