Israel Medical Association Journal

Background: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. 

Objectives: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis.

Methods: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis.

Results: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. 

Conclusions: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation. 

 

Background: In Israel a general code of ethics exists for physicians, drafted by the Israel Medical Association. The question arises whether psychiatrists require a separate set of ethical guidelines.

Objectives: To examine the positions of Israeli psychiatrists with regard to ethics in general and professional ethics in particular, and to explore opinions regarding a code of ethics or ethical guidelines for psychiatry. 

Methods: A specially designed questionnaire was compiled and completed by psychiatrists recruited for the study. 

Results: Most participants reported low levels of perceived knowledge regarding ethics, professional ethics, and the general code of ethics. Older and more experienced professionals reported a higher level of knowledge. Most psychiatrists agreed or strongly agreed with the need for a distinct code of ethics/ethical guidelines for psychiatrists. This support was significantly higher among both psychiatrists under 50 years and residents. 

Conclusions: Our findings suggest that the existing code of ethics and position papers may not be sufficient, indicating a potential need to develop and implement a process to create the ethical code itself. In addition, the findings highlight the importance of ethics education, suggesting that the need for a code of ethics is more urgent in the early stages of professional training, as younger professionals may be more exposed to advanced media technology. While some may fear that a distinct code of ethics will distance psychiatry from modern medicine, others assert that the profession combines aspects from the humanities and social sciences that require a unique sort of management and thus this profession requires a distinct code of ethics.

 

Background: Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM). 

Objectives: To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.

Methods: We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.

Results: VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.

Conclusions: Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.

 

Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix®, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1)pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed “black box” attitude towards all vaccines. The focus of this review article is to revisit this “black box” using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Background: Medical evaluation of a suspected meniscus injury begins with a history-taking and physical examination. Suspected meniscus injuries not responding to treatment are usually sent for imaging to confirm the diagnosis before arthroscopy. Tc-MDP bone single photon emission computed tomography (SPECT) scan has been suggested as an alternative to magnetic resonance imaging (MRI) in evaluating suspected knee meniscus tears.

Objectives: To examine the accuracy of knee SPECT as a tool to identify meniscus tears versus that of MRI as compared to the gold standard of arthroscopy.

Methods: The Israel Defense Forces database for 2005 through 2009 was searched according to the key words knee MRI, knee SPECT and knee arthroscopy. We identified 330 subjects who had undergone both a single knee SPECT and a single knee MRI prior to knee surgery. The medical files of 193 of the 330 subjects were randomly selected for review. A comparison was made between the preoperative SPECT and MRI studies and the arthroscopic finding. The sensitivity, specificity and accuracy were calculated.

Results: The subjects’ age was 21.3 ± 3.9. The agreement between SPECT and arthroscopy was 0.14 for the medial meniscus and 0.29 for the lateral meniscus. The agreement between MRI and arthroscopy was 0.59 for the medial meniscus and 0.69 for the lateral meniscus. SPECT scan was found to be 61% sensitive, 54% specific and 58% accurate in detecting common knee pathology, whereas MRI was found to be 95% sensitive, 67% specific and 85% accurate.

Conclusions: Knee SPECT has a lower sensitivity, specificity and accuracy than MRI in evaluating meniscal injuries and its use can result in increased unnecessary surgery.