Israel Medical Association Journal

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Autoimmune diseases constitute a diverse group of disorders characterized by cellular and humoral responses against self. The humoral autoimmune responses are directed against various cellular and extracellular components. These responses are highly specific for each autoimmune disease and result in the production of autoantibodies that characterize certain disease entities, representing a valuable tool for the diagnosis of autoimmune diseases. Furthermore, certain autoantibodies are helpful in the prognosis of disease development, progression and severity, as well as in the classification of patients with distinct disease subtypes. Today, the value of autoantibodies in the follow-up of patients is limited, but preliminary data suggest that they may be useful in predicting response to treatment. 

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Background: Upper respiratory tract infection (URTI) occurs frequently in the general population and is considered a benign self-limited disease. Dialysis patients constitute a high risk population whose morbidity and mortality rate as a result of URTI is unknown. 

Objectives: To assess the local incidence, morbidity and mortality of URTI in dialysis patients compared to the general population. 

Methods: In this retrospective cohort study we reviewed the charts of all chronic dialysis patients diagnosed with URTI at Meir Medical Center, Kfar Saba, Israel during the 2014–2015 winter season. 

Results: Among 185 dialysis patients, 40 were found to be eligible for the study. The average age was 66.1 ± 15.7 years, and the co-morbidity index was high. Influenza A was the most common pathogen found, followed by rhinovirus, respiratory syncytial virus and para-influenza. Of the 40 patients 21 (52.5%) developed complications: pneumonia in 20%, hospitalization in 47.5%, and respiratory failure requiring mechanical ventilation in 12.5%. Overall mortality was 10%. General population data during the same seasonal period showed a peak pneumonia incidence of 4.4% compared to 20% in the study population (P < 0.0001). 

Conclusions: The study findings show that compared to the general population, URTI in dialysis patients is a much more severe disease and has a higher complication rate. Influenza A, the most common pathogen, is associated with a worse prognosis. 

 

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. 

Immune function is the most basic physiological process in humans and indeed throughout the animal kingdom. Interestingly, the vast majority of textbooks of physiology do not include a chapter on immunity. Our species survival is dependent on the diversity of the immune response and the ability for antigen presentation and effector mechanisms to be enormously promiscuous. As physicians, we are likely all too aware of how brief our life span is and the myriad of diseases and events that shorten it. It is not surprising that we question where our life comes from and our relationship within the universe. Many hypotheses have been offered regarding the likelihood that intelligent life exists elsewhere. We propose that such issues be discussed in the context of basic biologic observations on earth, such as the sight of a dense flock of tens of thousands of starlings maneuvering in rapid twists and turns at dusk before settling in trees for the night. The mathematical likelihood for life elsewhere was proposed by Frank Drake in a classic equation whose 'thesis' has stimulated the search for alien civilizations and the nature of life. A fundamental gap in this equation is the presence of a diverse immune response, a feature essential for survival of Life, presumably also extra-terrestrially.

Background: Frailty is a dynamic process with transitions over time.

Objectives: To examine frailty transitions and their relationship to utilization of health services. 

Methods: Frailty status using the Vulnerable Elders Survey (VES-13) was determined for 608 community-dwelling older people interviewed in a 2008 national survey and for 281 re-interviewed in 2014. The effect of frailty on death 6 years later was assessed using Cox proportional hazards analysis. Participants were divided into four groups based on their frailty transition. Demographic, functional and health characteristics were compared between the four groups using the Kruskal-Wallis and paired t-test. The independent association between the four frailty groups and health services utilization was assessed using logistic regression. 

Results: Between 2008 and 2014, 24% of 608 participants were lost to follow-up, 9% were non- frail, 37% were frail, and 30% died. The Cox ratio showed that 86% of the non-frail in 2008 were alive 6 years later vs. 52% of the frail (hazard ratio 3.5, confidence interval 2.2–5.4). Frailty transitions in the 281 participants interviewed at both time points revealed that 19% stayed non-frail, 22% became frail, 22% stayed frail and 37% became more frail. Becoming frail, staying frail or becoming more frail compared to staying non-frail was independently associated with a greater risk for requiring help on a regular basis, having a formal caregiver, and requiring home care. 

Conclusions: Any transition away from the non-frail state increased the use of health care services. Interventions to target early transition to frailty should be encouraged.

 

Background: Chronic urticaria (CU) is a common disabling disorder. The CU-Q2oL (Chronic Urticaria Quality of Life Questionnaire) is a specific questionnaire for evaluating quality of life in CU patients. It consists of 23 items divided into six quality-of-life dimensions. It was initially developed in Italy and later validated in other countries.

Objectives: To validate and adapt the CU-Q2oL to the Hebrew language in order to make it suitable for use in Israel. 

Methods: The CU-Q2oL questionnaire was translated to Hebrew. A group of 119 CU patients were asked to complete this version, in addition to the Dermatology Life Quality Index (DLQI) and Urticaria Activity Score (UAS) questionnaires. A factorial analysis was performed to identify CU-Q2oL subscales, internal consistency and convergent validity assessment, as well as factors determining quality-of-life scores.

Results: The factor analysis identified six scales of the Israeli CU-Q2oL: (i) sleep and concentration, (ii) function and mental status, (iii) embarrassment and clothing limitations, (iv) itching, (v) eating behavior and medication side effects, and (vi) swelling, which accounted for 77% of the data variance. Five scales showed good internal consistency over 0.81. The mean ± SD score of CU-Q2oL in our patients with CIU was 41 ± 21.7. We found a strong positive correlation between the overall scores of CU-Q2oL and DLQI questionnaires (r = 0.8, P < 0.01). Additionally, we found a positive correlation between UAS and both CU-Q2oL and DLQI (r = 0.62, P < 0.01, and r = 0.53, P < 0.01, respectively). 

Conclusions: This study demonstrates that the Israeli CU-Q2oL questionnaire is suitable for both clinical use and research in Israel.

 

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

Background: The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. 

Objectives: To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone.

Methods: We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was “immediate treatment versus delayed treatment.” All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa Maria da Feira. The main outcome measure was the HAQ-DI; the moderated regression analysis, together with the Johnson-Neyman technique, was used for statistical analysis.

Results: HAQ-DI at the end of treatment (21 days) and at the 3 month follow-up was improved in the spa group (odds ratio 0.37, confidence interval 0.09–0.64, P = 0.01 at 21 days, and 0.44, 0.15–0.72, P = 0.004 at 3 months).

Conclusions:

Background: Bioresorbable vascular scaffold (BVS) is a promising technology that potentially offers several advantages over contemporary coronary drug-eluting stents (DES). Crucial to BVS implantation is the correct choice of scaffold size (diameter and length) in order to avoid "geographic miss" in length, provide the maximal support to the vessel wall, and avoid leaving “free-floating” foreign material in the coronary vasculature. 

Objectives: To assess the optimal method for measuring coronary stenosis prior to BVS implantation.

Methods: We compared the performance of two quantitative coronary angiography assessment (QCA) techniques: two dimensional real-time QCA (2D-QCA) and offline 3D QCA (3D-QCA) for the evaluation of coronary lesions in patients enrolled in a multicenter randomized controlled trial of BVS vs. metallic stents, by calculating the weighted kappa value for agreement regarding optimal BVS size with the reference method – CoreLab offline 2D-QCA measurements..In addition, we collected 2 year clinical outcomes (death/myocardial infarction/repeat revascularization/scaffold thrombosis) in BVS-implanted patients.

Results: In 17 patients with available CoreLab data, the weighted kappa for agreement for 3D-QCA was significantly better than for 2D-QCA (0.90, 95%CI 0.72–1.00 vs. 0.439, 95%CI 0.16–0.77). The rate of clinical events at 2 years was low (9.5%).

Conclusions: Initial experience in a small group of carefully selected patients at our institution, suggests that the use of BVS for coronary revascularization is associated with a low rate of adverse events in suitable patients. 3D-QCA may be superior to 2D-QCA analysis in terms of reproducibility, and results in more patients receiving optimal size BVS. 

 

Background: Due to a shortage of individualized erythromycin ointment (IEO), we switched to shared erythromycin drops (SED). Following this change, nurses claimed observing more cases of eye discharge. 

Objectives: To test whether switching from IEO to SED affected the rate of neonatal conjunctivitis (NC).

Methods: The study group included 14,916 neonates > 35 weeks of gestation, further divided into two birth periods of 12 months each: 1 January 2013 to 31 December 2013 (IEO) and 1 February 2014 to 31 January 2015 (SED). We compared the two birth periods with regard to three variables: clinical NC (number of conjunctival swabs/1000 neonates), bacterial NC (number of culture-positive swabs/1000 neonates), and bacterial growth percentage (number of culture-positive swabs/100 samples).  

Results: Compared to 2012–2013, the period 2014–2015 included fewer cesarean deliveries and shorter length of stay (LOS). Clinical NC, bacterial NC and bacterial-growth percentage were not different between the two periods. Variables that were independently significantly associated with increased clinical NC included male gender (OR 1.48, CI 1.21–1.81) and LOS (OR 1.24, CI 1.18–1.29). LOS was associated with bacterial NC (OR 1.19, CI 1.11–1.28). Coagulase-negative staphylococci, Escherichia coli and Pseudomonas aeruginosa were the prevalent pathogens, though without difference between periods. 

Conclusions: Rates of clinical NC, bacterial NC and bacterial-growth percentage were not different between the study periods. Switching from IEO to SED had no effect on the NC rate.