Israel Medical Association Journal

Background: Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the course of the disease and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.

Objectives: To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.

Methods: We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.

Results: Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P < 0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.

Conclusions: Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment. 

Background: New animal models provide insights into the pathogenesis of different types of inflammatory bowel disease as well as novel pathways for new therapeutic options. However, the scarcity of large animal models hinders the research and development of new surgical procedures and technological devices in inflammatory bowel disease surgery. Common small animal inducible models involve chemical agents that result in the development of acute intestinal inflammation.

Objectives: To assess a novel method for the induction of Crohn’s-like colitis using intramural injection of sclerosants in a porcine model.

Methods: Seven domestic pigs underwent several experimental protocols to assess the efficacy of intramural colonic injections of two different compounds (lauromacrogol, and phenol in almond oil). Twenty-five different large bowel segments were treated with intramural injections of the compounds. The animals were followed for 6 weeks, and treated colonic segments were resected for histopathological examination.

Results: Intramural injection of lauromacrogol resulted in non-specific, mild reactive foreign body changes only. Injection of various dosages of 5% phenol in almond oil caused a range of histopathological changes varying from focal fibrosis to Crohn’s-like reactions comprising acute and chronic infiltrates, mucosal ulceration and focal necrosis with enteric and lymphoid non-caseating granulomas.

Conclusions: Intramural colonic phenol in almond oil injection in pigs induces inflammatory reactions that histologically resemble Crohn's disease in humans. 

Background: Most spine tumors are resistant to radiation and chemotherapy. Complete surgical removal provides the best chance for long-term control of the tumor. Total en bloc spondylectomy (TES) is a radical new technique that entails total removal of the tumor and affected vertebras with clean margins.

Objectives: To review our initial experience with TES, focusing on feasibility, surgical challenges and the short-term outcome.

Methods: We retrospectively reviewed the hospitalization charts and follow-up data of all patients treated with TES for spine tumors in the spine unit at Tel Aviv Medical Center.

Results: TES was performed in 12 patients aged 13–78 years. Nine patients had primary spinal tumors and three had metastasis. Total en bloc removal was achieved in all cases with spondylectomy of one to three affected vertebras. There was no perioperative mortality and only one major intraoperative complication of injury to a major blood vessel. Late complications were mainly related to hardware failure.

Conclusions: Total en bloc spondylectomy is feasible and effective for the management of selected patients with extradural spinal tumors. Since the surgical procedure is demanding and carries significant risk, careful preoperative evaluation and collaboration with colleagues from other specialties are crucial.

We are overwhelmed by warnings about inevitable geophysical and human problems. Earth is beset by escalating, man-made, environmental crises and our exploding population will eventually lack water, food and vital materials. This suggests, together with increasing poverty, deepening social unrest and advanced techniques for mass killing, that civilization will break down long before atmospheric CO₂ or resistant microbes become catastrophic. Despite intensive searching, life has not been found in space, even though thousands of planets have been found and life there may be as problematic and unpredictable as on Earth. The human brain is already a 'universe', with 85 billion neurons and a hundred trillion synapses, more than the stars in our galaxy. Understanding consciousness, the brain, its aging and pathologies, and eliminating the propensity for human aggression are urgent challenges. During 1958–2012, NASA spent $800 billion. In contrast, the annual cost of brain disease in the U.S. is $600 billion, more than cardiovascular disease and cancer combined. We suggest that a massive switching of financial and human resources is required to explore the full potential of the human brain. Visiting Mars can wait. We further propose a novel two-brain hypothesis: the animal 'brain' evolved as two fundamentally different though interdependent, complementary organs: one electroionic (tangible, known and accessible), and the other, electromagnetic (intangible and difficult to access) – a relatively independent, stable, structured and functional 3D compendium of variously induced interacting EM fields.

Background: A clavicular fracture accounts for 2.6%–5% of adult fractures. Fractures in the middle-third (OTA 15-B) represent 69%–82% of all clavicular fractures. There is no consensus among orthopedic surgeons regarding treatment for these fractures; many support conservative treatment even for displaced middle-third clavicular fractures, while others choose operative treatment.

Objectives: To assess the attitudes of orthopedic surgeons regarding treatment of displaced mid-shaft clavicular fractures.

Methods: We conducted a survey in which we interviewed orthopedic surgeons from various countries during the 2012 EFORT meeting in Berlin. The questionnaire included an X-ray of a displaced middle-third clavicular fracture, as well as questions regarding the surgeon’s proposed treatment plan.

Results: A total of 177 orthopedic surgeons completed the questionnaire; 49% preferred operative treatment for a displaced middle-third clavicular fracture. Among the orthopedic trauma specialists, 58% suggested operative treatment, as did 82% of shoulder specialists. Most surgeons preferred a locking plate for fixation.

Conclusions: The treatment approach for a displaced middle-third clavicular fracture seems to be evenly split between conservative and operative approaches. The tendency toward operative treatment was even more remarkable among orthopedic trauma specialists and shoulder specialists who completed the questionnaire. Most surgeons prefer a locking plate as a fixation system for this type of fracture. 

Background: The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.

Objectives: To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.

Methods: The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n=205), intermediate 22–31 (n=138), and high ≥ 32 (n=63). Five year mortality was derived from the National Mortality Database.

Results: Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P < 0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P < 0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.

Conclusion: Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.

Background: Trachea esophageal puncture (TEP) is performed following total laryngectomy to allow speech and communication. The most common reason for long-term speech failure in this population is hypertonicity of the constrictor muscle.

Objectives: To present our experience with the treatment of aphonic patients after total laryngectomy and TEP and suggest a protocol for treatment.

Methods: Of 50 patients who underwent total laryngectomy and TEP, 6 suffered from aphonia after surgery. All patients underwent radiotherapy with or without chemotherapy. Delay in speech continued for more than 6 months after surgery. The patients received percutaneous lidocaine injection to the neopharynx in different locations around the stoma in order to map the hypertonic segments in the neopharynx.

Results: Lidocaine injection immediately enabled free speech in five patients. One patient (patient 6) suffered from aphonia and from severe dysphagia and required a feeding tube. This patient succeeded to pronounce abbreviations after lidocaine injection. Another (patient 4) gained permanent ability to speak following a single lidocaine injection; this patient was not injected with botolinium toxin (BTX). For the other five, lidocaine had a transient effect on speech. These patients received BTX percutaneous injections. After BTX injections four regained free speech within 14 days. The fifth patient (patient 6) gained a conversational voice and experienced improvement in swallowing only after additional intensive speech therapy.

Conclusions: Percutaneous lidocaine and BTX injections represent first-line treatment in this population, with good success and minimal complications. 

Background: Intra-articular corticosteroid injection (IACI), a common procedure in juvenile idiopathic arthritis, is usually associated with anxiety and pain. In a previous study, we concluded that nitrous oxide (NO₂) provides effective and safe sedation for such procedures. Following the introduction of medical clowns in our hospital, we added them as an integral part of the team performing IACI.

Objectives: To prospectively evaluate the effect of a medical clown on pain perception during intra-articular corticosteroid injection for juvenile idiopathic arthritis using NO₂ conscious sedation.

Methods: Patients scheduled for IACI first met and interacted with the medical clown. During the procedure, the rheumatologist and the medical clown worked in parallel to create distraction. NO₂ was administered. The patient, parent, physician, medical clown and nurse completed a visual analog scale (0–10) for pain. Change in heart rate ≥ 15% was recorded to evaluate physiologic response to pain and stress.

Results: A total of 46 procedures were performed in 32 children: 23 girls, 9 boys, with a mean age of 10.9 ± 3.6 years. The median visual analog scale pain score for the patients, parents, physicians, medical clown and nurses was 2, 2, 1, 1 and 1, respectively. Five patients had increased heart rate and experienced increased pain.

Conclusions: Active participation of a medical clown during IACI with nitrous oxide for juvenile idiopathic arthritis further decreases pain and stress and results in a positive patient experience. 

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).

Emerging and re-emerging infections cause huge concern among public health workers and international and national bodies such as the World Health Organization (WHO) and the U.S. National Institutes of Health (NIH). Indeed, scientists around the world express the view that despite the danger, research on these emerging virulent pathogens is crucial and must continue. While most of the studies underway are targeted at improving and protecting public health, some studies bear potentially serious risks resulting from misuse. These studies are defined as dual-use research (DUR) of concern, where it is not evident that the benefits outweigh the risks. The H5N1 controversy has pushed various governments to institute new policies to govern such research. We describe the regulations that govern this emerging field of research in the United States and Israel, two countries that have taken leading stands on these issues. We suggest that the existing policies are able to mitigate many of the risks that this research encapsulates, yet more work is required – especially on the global level.