Israel Medical Association Journal

Background: Methotrexate is the most frequently administered first-line treatment for rheumatoid arthritis (RA). The disease-modifying effects of methotrexate are mainly associated with enhanced release of free adenosine. The downstream anti-inflammatory effects of adenosine are mediated via its binding to adenosine receptor 2A (ADORA2A) and 3 (ADORA3). Many clinically important single nucleotide polymorphisms (SNPs) were reported in ADORA2A and ADORA3 genes.

Objectives: To investigate whether tagging ADORA2A and ADORA3 polymorphisms influences methotrexate treatment in RA.

Methods: In total, 212 RA patients treated with methotrexate were genotyped for tagging ADORA2A (rs2298383, rs8141793, rs2236624, rs5751876, rs35320474, and rs17004921) and ADORA3 SNPs (rs2298191, rs1544223, rs78594984, rs35511654, rs2229155, rs3393, and rs3394).

Results: RA patients who carried ADORA3 rs35511654 G allele showed a tendency toward better response to methotrexate treatment (P = 0.054). Carriers of ADORA2A polymorphic allele rs2298383 (P = 0.011), rs2236624 (P = 0.027), rs5751876 (P = 0.018), and rs35320474 (P = 0.026) were less likely to experience methotrexate induced adverse events. All associations remained significant after adjustment for clinical factors. The effects of these polymorphisms were also significant in haplotype analyses.

Conclusions: Polymorphisms in the ADORA2A gene may influence methotrexate treatment response and may be considered as a potential biomarker for methotrexate treatment in rheumatoid arthritis.

Background: The prevalence of Helicobacter pylori varies geographically by age, race, and socioeconomic status (SES). However, the impact of ethnicity on endoscopic outcomes in infected individuals is not well known.

Objectives: To assess the impact of ethnicity among Israelis with biopsy-proven H. pylori infection.

Methods: A retrospective study, including patients who underwent gastroscopy and were diagnosed histologically with H. pylori infection, was conducted. Information on demographics, SES, medications, and co-morbidities were extracted from medical records. Univariate (Student's t-test, chi-square test) and multivariate (multinomial and logistic) regression analysis were conducted to examine the predictors of the clinical outcome.

Results: The study included 100 Israeli Jews and 100 Israeli Arabs diagnosed with biopsy-proven H. pylori infection. At univariate analysis, the number of households was higher among Arabs (P < 0.001), whose family income and parental education were lower than among Jews (P < 0.001 for both variables). The response to amoxicillin and clarithromycin differed between the two groups, being higher among Jews (P < 0.001).In clinical outcomes (gastritis severity, gastric and duodenal ulcer, intestinal metaplasia, atrophic gastritis, and MALT), no statistically significant differences could be detected between Jews and Arabs. Concerning intestinal metaplasia, lack of consumption of nonsteroidal anti-inflammatory drugs resulted a statistically significant protective factor (odds ratio 0.128, 95% confidence interval 0.024–0.685, P = 0.016).

Conclusions: Although in the literature ethnicity seems to be a risk factor for H. pylori colonization, no statistical significance was detected in various endoscopic and histological findings related to H. Pylori infection between Israeli Arabs and Jews.

Angiogenesis is the outgrowth of new blood vessels from existing ones and is an early occurrence in inflamed joint tissue. It is governed by a tightly controlled balance of pro- and anti-angiogenic stimuli, which promote or inhibit generation and proliferation of new endothelial cells, vascular morphogenesis, and vessel remodeling. At the beginning, capillary formation is crucial in maintaining the supply of various nutrients as well as oxygen to the inflamed tissue. Local and systemic expression of angiogenic factors may indicate a constant remodeling of synovial vasculature. Redox signaling is closely related to angiogenesis and can alter angiogenic responses of synovial cells. In this review we discuss key issues about the endothelial pathology in inflammatory arthritis followed by a review of angiogenic processes and main angiogenic mediators. We discuss the hypoxia-vascular endothelial growth factor (VEGF)-Ang/Tie2 system and its related therapeutic implications in detail with further review of various mediator protein targets and intracellular regulatory pathway targets with their current and potential future role in preclinical or clinical setting whilst ameliorating inflammation.

Throughout history, studies on episodes of famine have led to the discovery of metabolic abnormalities and hormonal aberrations as well as an increased incidence of cancer and mental health conditions. Starvation during early life is thought to nfluence the programming of childhood and adult bone metabolism, which may result in poor bone health in later life. This observational case series includes a small group (with no control group) of famine-exposed Holocaust survivors and their descendants. We proposed an investigational mechanism to determine any association between starvation and osteoporosis, both in the individual survivors and in their descendants.

Background: Kidney transplantation is associated with early improvement in cardiac function and structure; however, data on cardiac adaptation and its relation to kidney allograft function remain sparse.

Objectives: To investigate the relationship between post-transplant kidney function and echocardiographic measures in patients with normal/preserved pre-transplant cardiac structure and function.

Methods: The study included 113 patients who underwent kidney transplantation at a single tertiary medical center from 2000 to 2012. The patients were evaluated by echocardiography before and after transplantation, and the relation between allograft function and echocardiographic changes was evaluated. Echocardiography was performed at a median of 510 days after transplantation.

Results: The post-transplantation estimated glomerular filtration rate (eGFR) was directly correlated with left ventricular (LV) systolic function and inversely correlated with LV dimensions, LV wall thickness, left atrial diameter, and estimated systolic pulmonary arterial pressure. In patients with significant allograft dysfunction (eGFR ≤ 45 ml/min), LV hypertrophy worsened, with no improvement in LV dimensions. In contrast, in patients with preserved kidney function, there was a significant reduction in both LV diameter and arterial pulmonary systolic pressure.

Conclusions: Our results show that in kidney transplant recipients, allograft function significantly affects cardiac structure and function. Periodic echocardiographic follow-up is advisable, especially in patients with kidney graft dysfunction.

Background: When a woman with an endometrioma presents with acute abdominal pain, it is unclear whether ovarian torsion should be suspected.

Objectives: To compare patient characteristics, imaging results, and surgical management of endometriomas in elective versus emergent surgeries.

Methods: This retrospective cohort study included women treated at our institution during the period 1990–2015 who presented with histologically verified endometrioma and who underwent either planned surgery or emergent surgery due to suspected adnexal torsion.

Results: Of 225 surgeries performed, 174 were elective and 51 emergent. Patients in the emergent group were significantly younger (33.9 ± 11.1 vs. 39.01 ± 10.9 years, P = 0.004). Abdominal pain was the main complaint of all the emergent surgery patients and the leading complaint in 21% of the elective surgery patients (P < 0.001), with right-sided predominance in both groups. Sonographic parameters were similar in both groups. Bilateral ovarian cysts were noted in 11.7% and 11.0% of emergent and elective patients, respectively (P = 0.87). Laboratory evaluation was notable for a higher white blood cell count and CA125 levels among emergent patients. All patients in the emergent group and 93% of patients in the elective group were managed laparoscopically. No cases of torsion were noted. The rate of intra-pelvic adhesions was similar in both groups (56.8% vs. 66.6%, P = 0.19).

Conclusions: Endometrioma may present with acute abdominal pain. However, adnexal torsion in these patients is rare. These cases can be managed using a minimally invasive approach, assuming an optimal surgical setting.

Background: Multidisciplinary biopsychosocial rehabilitation for patients presenting with rheumatic diseases has been shown to produce better results in a warm climate. Dead Sea Climatotherapy (DSC) has been successfully used for decades to treat many patients with rheumatic diseases.

Objectives: To evaluate the short-term improvement of Norwegian patients who presented with chronic pain following a multidisciplinary biopsychosocial approach to treatment combined with DSC. Both objective and subjective clinical parameters were evaluated.

Methods: This retrospective study included a statistical analysis of 938 patients presenting with rheumatoid arthritis and ankylosing spondylitis (n=105), osteoarthritis (n=342), fibromyalgia (n=374), and other orthopedic conditions (n=117). Clinical assessments were conducted before and after a 3 week treatment program at the Dead Sea.

Results: Six parameters improved significantly in the rheumatoid arthritis and ankylosing spondylitis group as well as in the osteoarthritis group. Five parameters in the fibromyalgia group improved, while two improved in the orthopedic conditions group. Overall, major significant changes occurred in the pain self-assessment, joint motility, and daily activities scores.

Conclusions: A 3-week multidisciplinary biopsychosocial program combined with DSC induced positive changes in the clinical parameters of Norwegian patients presenting with chronic musculoskeletal pain.

Background: Lower extremities ulcers (LEU) are associated with considerable morbidity and mortality. With longer life expectancy, the prevalence of LEU in developed countries is assumed to grow, necessitating an increased demand for treatment by specialists. 

Objectives: To compare the effectiveness of a telemedicine video conferencing modality with the conventional face-to-face treatment of LEU. 

Methods: The study was conducted in conjunction with a two-million member healthcare organization in Israel (Maccabi Healthcare Services). Consecutive visits of patients to wound care specialists during a 12-month observation period reviewed in 2015 were valuated. A nurse-assisted setting was implemented during all treatment sessions. The same specialist supervised patients in both modalities. 

Results: A sample of 111 patients (n=55 in the telemedicine group; n=56 in the face-to-face group) with 593 visits was analyzed. No significant difference in healing of LEU (78.2% in telemedicine vs. 75.0% in face-to-face) was detected, P = 0.823. A reduced number of visits in telemedicine (4.36 ± 2.36) compared to the face-to-face care (6.32 ± 4.17) was shown, P = 0.003. Non-inferiority of telemedicine demonstrated within the Δ = 15% range limits and 80% statistical power was demonstrated. 

Conclusions: Compared to the usual face-to-face method, synchronous video conferencing-based telemedicine may be a feasible and efficient method for LEU management. 

 

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: Horse riding has become increasingly popular in recent years and is a common activity among children. As a result, pediatric horse-related injuries are frequently encountered in emergency departments.

Objectives: To examine the characteristics of horse-related injuries in the pediatric population.

Methods: We collected and analyzed the data on all pediatric horse-related injuries presented to a tertiary hospital, level one trauma center, during the years 2006–2016.

Results: A total of 53 children with horse-related injuries were documented. Forty-two patients were male (79%) and their mean age was 11.13 ± 4.72 years. The most common mechanism of injury was falling off a horse (31 patients, 58%) and the most common type of injury was skeletal (32 patients, 60%). Head injuries occurred in 16 patients (30%) and facial injuries in 12 (23%). The mean Injury Severity Score (ISS) was 10.5 ± 6.32, and 15 patients (28%) had severe trauma (ISS > 15). Twenty-nine patients (55%) required trauma team intervention, 12 (23%) were admitted to the intensive care unit, and 24 (45%) required surgery. The mean length of hospitalization was 4.3 ± 3.14 days.

Conclusions: Our study suggests that horse-related trauma may involve serious injuries and it exhibits typical injury patterns. Young boys are at highest risk. The potential severity of these injuries merits a thorough evaluation. We suggest that these injuries be triaged appropriately, preferably to a medical facility with proper trauma capabilities.