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עמוד בית
Wed, 13.11.24

December 2014


Perspective
Geoffrey Goodman PhD, M. Eric Gershwin MD and Dani Bercovich PhD

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.

Original Articles
Yaron S. Brin MD, Ezequiel Palmanovich MD, Eran Dolev MD, Meir Nyska MD and Benyamin J. Kish MD

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. 

Vera Stejskal PhD
Background: The multiple symptoms of chronic fatigue syndrome (CFS) and fibromyalgia resemble those described in patients suffering from autoimmune/inflammatory syndrome induced by adjuvants (ASIA). It has been suggested that chronic metal-induced inflammation might play a role both in CFS and fibromyalgia as well as in ASIA. Humans are exposed to metals mainly through the release of metal ions from corroding dental restorations and orthopedic implants, food, vaccines and jewelry. Metals readily bind to sulphur and other groups in the mitochondria, enzymes and cell proteins. Metal-bound proteins are recognized by the immune system of susceptible subjects and might trigger an abnormal immune response, including allergy and autoimmunity.

Objectives:  To study three subjects with CFS and two with fibromyalgia, all of whom suspected metal exposure as a trigger for their ill health.

Methods: We measured delayed-type hypersensitivity to metals (metal allergy) using a validated lymphocyte transformation test, LTT-MELISA®. All patients except one were sensitized to metals present in their dental restorations. The remaining patient reacted to metals in his skull implant. The removal of sensitizing metals resulted in long-term health improvement. Nine healthy controls matched for gender and age showed only marginal reactivity to the metals tested.

Conclusions: Patients with CFS and fibromyalgia are frequently sensitized to metals found in the environment or used in dentistry and surgery. This allergy to metals might initiate or aggravate non-specific symptoms in metal-sensitized patients.
Yehoshua Shapira DMD, Itay Blum DMD, Ziona Haklai MSc, Nir Shpack DMD and Yona Amitai MD MPH

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Results: Of 976,578 liveborn infants, 684 presented unilateral or bilateral clefts, with a prevalence of 7.00/10,000 live births; 479 were Jews and 205 were Arabs. The prevalence was higher among Arabs compared to Jews (11.12 and 6.22 per 10,000 live births in Arabs and Jews, respectively, P < 0.00001). Males had higher cleft rates than females (7.69/10,000 and 6.17/10,000 live births, respectively, P = 0.05). Males had more cleft lips with or without cleft palate, while females had more isolated cleft palates


(P < 0.001). There was left-side predominance. Newborns of younger mothers (age < 20 years) and of older mothers (age ≥ 45 years) had higher cleft rates than those with mothers in the 20–44 year bracket (P < 0.009). Children born at or above the 5th birth order had a higher cleft rate (P < 0.001).


Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Sharon Gannot MD, Paul Fefer MD, Eran Kopel MD, Ksenia Kuchkina MD, Roy Beigel MD, Ehud Raanani MD, Ilan Goldenberg MD, Victor Guetta MD and Amit Segev MD

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.

Limor Benyamini MD MSc, Ziv Gil MD PhD and Jacob T. Cohen MD

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. 

Yael Weintraub MD, Noa Rabinowicz MD, Penny Hanuka, Michal Rothschild MD, Shulamit Kotzki and Yosef Uziel MD

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. 

Nira Varda-Bloom PhD, Avraham J. Treves PhD, Tatiana Kroupnik MSc, Dan Spiegelstein MD, Ehud Raanani MD and Arnon Nagler MD

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).

Editorials
Orna Steinberg Shemer MD MSc and Hannah Tamary MD
Reviwes
Borys A. Cornejo-Moreno MD MSc, Diego Uribe-Escamilla MD and Fabio Salamanca-Gómez MD
Breast cancer, specifically mammary carcinoma, is the most common cause of death from cancer in women worldwide, with a lifetime risk of one in nine, and its prevalence is increasing. It represents around 30% of all cancer in females and approximately 40,000 deaths in the United States per year. Important advances have been made in detection and treatment, but a significant number of breast cancers are still detected late. This summary of its epidemiology and history, the molecular aspects of detection and the main implicated genes emphasizes the etiology and heterogeneity of the disease. It is still not clear whether the remaining cases of breast cancer negative to BRCA are due to mutations in another high penetrance gene or to unknown factors yet to be discovered.
Zahava Vadasz MD, Doron Rimar MD and Elias Toubi MD
Case Communications
Ronit Marcus MD, Eli Shiloah MD, Avi Mizrahi MD, Osnat Gerah-Yehoshua and Micha J. Rapoport MD
Eilon Krashin MD, Michael Lishner MD, Michal Chowers MD and Sharon Reisfeld MD
Alessandra Soriano MD, Ribhi Mansour MD, Yuval Horovitz MD and Howard Amital MD MHA
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