Israel Medical Association Journal

Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin®) and ranibizumab (Lucentis®) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.

Objectives: To describe the current application of anti-VEGF[1] drugs among retinal specialists in Israel.

Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.

Results: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient’s socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series if the first one yielded no improvement in fluid status. The routine practice for intravitreal injection (> 80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.

Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies.  

Background: Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial.

Objectives: To assess the approach of leading pediatric specialists throughout Israel.

Methods: A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI[1], according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel.

Results: Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72–75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists.

Conclusions: The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to up-to-date evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

Background: Multiple drug allergy syndrome is a rarely reported clinical condition characterized by an adverse reaction to more than one different class of pharmacologically and structurally unrelated drugs. The pathogenesis may involve immediate-type or delayed-type hypersensitivity.

Objectives: To further characterize patients with MDA[1] in terms of the type of CADR, drug intake and clinical drug suspicion.

Methods: The study group comprised 12 patients (6 males, 6 females) with CADRs[2] showing in vitro drug-induced IFNγ[3] release for multiple drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNγ release in identifying the culprit drugs was evaluated in terms of clinical data and the results of in vivo tests (withdrawal and/or challenge tests) with the offending drugs.

Results: Clinical relevance was attributed to in vitro drug-induced IFNγ release towards multiple drugs in this series of 12 patients with a variety of CADRs, implying MDA. The results of in vivo tests for the offending drugs confirmed the diagnosis. The main causative agents responsible were antibiotics and non-steroidal anti-inflammatory drugs.

Conclusions: The study further supports the role of a T cell-mediated mechanism in the pathogenesis of MDA. The in vitro drug-induced IFNγ release test may serve as a laboratory tool to identify the culprit drugs associated with this allergy.  

Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger. OP[1] and CRB[2] poisoning is an important clinical problem, often life-threatening, especially in the pediatric population in rural areas where reaching a physician or hospital on time is difficult. We present a summary of accumulated toxicological knowledge as well as clinical and laboratory experience from a medical center serving a relatively vast rural area and pediatric population. We stress the importance of knowing how to recognize the classic signs of OP and CRB poisoning and when it is appropriate to investigate for such poisoning even in the absence of those signs. Like any medical emergency, OP and CRB poisoning requires prompt resuscitation and use of antidotes. Atropine, oxygen and fluids are the mainstay of therapy. Oximes, which were found useful in some cases of OP poisoning and useless in some cases of CRB poisoning, are absolutely safe as empiric treatment, which is often needed since the major differential diagnosis of OP poisoning is CRB poisoning that is clinically indistinguishable. We hope that continuing research will offer further insights into the management of such events, and we are confident that improved medical management of OP and CRB poisoning will result in a reduction of morbidity and other complications associated with intensive care procedures and hospitalization. 

Background: Cardiac computed tomography scans influde several extra-cardiac structures such as mediastinum, lung parenchyma and upper abdominal organs. A variety of abnormalities in those structures might be clinically important and in some cases might explain the patient's complaints.

Objectives: To analyze consecutive cardiac computed tomography examinations for the prevalence and clinical significance of extra-cardiac findings.

Methods: Cardiac CT scans of 134 sequential patients (104 males, 30 females) aged 20–77 years (mean 54 years) with suspected coronary artery disease were prospectively and independently reviewed by a consensus of two radiologists for the presence of lung, mediastinal, pleural, upper abdominal and skeletal abnormalities. CT scans with extra-cardiac abnormalities were divided into two groups: group A – defined as "clinically significant" or "potentially significant findings" – consisted of patients requiring further evaluation or follow-up, and group B – "clinically non-significant findings."

Results: Extra-cardiac abnormalities were found in 103 of the 134 patients (76.8%). Group A abnormalities were found in 52/134 patients (39%), while group B abnormalities were seen in 85/134 (63%). The most common abnormalities in group A were non-calcified lung nodules (> 4 mm) noted in 17/134 patients (13%), followed by enlarged mediastinal lymph nodes (> 10 mm) in 14/134 (10%), diaphragmatic hernia (2 cm) in 12/134 (9%), moderate or severe degenerative spine disease in 12/134 (9%), and emphysema and aortic aneurysm in 6 patients each (4.5%). A malignant lung tumor was noted in one patient.

Conclusions: There is a high prevalence of non-cardiac abnormalities in patients undergoing CCT[1]. Clinically significant or potentially significant findings can be expected in 40% of patients who undergo CCT, and these will require further evaluation and follow-up. The reporting radiologist should be experienced in chest imaging and aware of the large variety of non-cardiac findings in CCT that might explain the patient's complaints. 

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: Idiopathic frozen shoulder is a self-limiting regional skeletal problem of unknown etiology. Clinically, patients first experience a phase of pain, progressing to a freezing stage when glenohumeral motion is lost, followed by a thawing phase when pain gradually subsides and most of the lost motion returns.

Objectives: To identify possible specific and non-specific risk factors for idiopathic frozen shoulder.

Methods: We compared the medical histories, drug treatment, previous hospital as well as health management organization blood tests of 126 new consecutive frozen shoulder patients from a shoulder clinic to those of an age-matched control group of 98 consecutive patients from an orthopedic foot and ankle clinic and to the regional population disease prevalence registry. Frozen shoulder was classified as idiopathic only if there was no history of trauma and no evidence of a rotator cuff tear.

Results: Among the frozen shoulder patients 29.4% had diabetes and 13.5% had thyroid disorders. The risk ratio for diabetes in the frozen shoulder group was 5.9 for males (95% confidence interval 4.1–8.4, P < 0.001) and 5.0 for females (95% CI[1] 3.3–7.5, P < 0.001). The risk ratio for thyroid disorders among females with frozen shoulder was 7.3 (95% CI 4.8–11.1, P = 0.001). No significant difference was found in the prevalence of thyroid disorders between frozen shoulder and the control group, but there was a significantly higher prevalence of diabetes in males and a trend for higher prevalence in females in the frozen shoulder group.

Conclusions: Physicians should be aware that diabetes is a specific risk factor for idiopathic frozen shoulder in both males and females and thyroid disorders are a non-specific risk factor in females only.