Israel Medical Association Journal

Uveal melanoma (UM) affects approximately six individuals per million per year in the United States, with similar rates in Mediterranean countries. Although it appears to have a low prevalence, it is the most common primary intraocular malignancy in adults. Clinically, it presents in most patients as a painless loss or distortion of vision, although it may also be accidentally discovered at routine ophthalmic examination. Associated risk factors include fair skin tone, light eye color, presence of a choroidal nevus, oculodermal melanocytosis (nevus of ota), dysplastic nevus syndrome, and germline BRCA-associated protein 1 mutations (BAP1 mutations) [1].

The prevalence of choroidal nevi associated with choroidal neovascular membrane (CNV) is estimated to range between 0.58% and 8.6% [1]. The pathogenesis of CNV is not completely understood. Researchers have suggested that damage caused to the choroid capillaries above the nevi affects the overlying retinal pigment epithelium and triggers production of angiogenic factors that, in turn, cause the development of CNV [2,3]. Hypoxia and inflammation may be involved in the process. Data have been inconsistent with both theories [4].

Background: Freeze dried plasma (FDP) is a commonly used replacement fluid in the prehospital setting when blood products are unavailable. It is normally administered via a peripheral intravenous (PIV) line. However, in severe casualties, when establishing a PIV is difficult, administration via intraosseous vascular access is a practical alternative, particularly under field conditions.

Objectives: To evaluate the indications and success rate of intraosseous administration of FDP in casualties treated by the Israel Defense Forces (IDF).

Methods: A retrospective analysis of data from the IDF-Trauma Registry was conducted. It included all casualties treated with FDP via intraosseous from 2013 to 2019 with additional data on the technical aspects of deployment collected from the caregivers of each case.

Results: Of 7223 casualties treated during the study period, intravascular access was attempted in 1744; intraosseous in 87 of those. FDP via intraosseous was attempted in 15 (0.86% of all casualties requiring intravascular access). The complication rate was 73% (11/15 of casualties). Complications were more frequent when the event included multiple casualties or when the injury included multiple organs. Of the 11 failed attempts, 5 were reported as due to slow flow of the FDP through the intraosseous apparatus. Complications in the remaining six were associated with deployment of the intraosseous device.

Conclusions: Administration of FDP via intraosseous access in the field requires a high skill level.

Background: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets.

Objectives: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis.

Methods: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019.

Results: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects.

Conclusions: The efficacy of MyC injection should be studied prospectively.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Drooling is the unintentional loss of saliva from the mouth, usually caused by poor coordination of the swallowing mechanism. It is commonly seen in patients with chronic neurologic disorders, such as Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral palsy, and stroke, as well as in patients with cognitive impairment and dementia.

Objectives: To evaluate the efficacy and safety of ultrasound-guided botulinum toxin injections into the parotid and submandibular salivary glands for the treatment of drooling.

Methods: We conducted a retrospective analysis of the medical records of 12 consecutive patients treated with botulinum toxin injections into the parotid and submandibular glands for the first time. The primary outcome variable was the subjective improvement of drooling on a 5-point scale. Secondary outcome variables were duration of the therapeutic effect, request to undergo additional treatment, and adverse events.

Results: Of 12 patients, 8 (67%) reported considerable improvement after treatment, 3 reported slight improvement, and 1 reported development of dry mouth. All patients stated that they felt the effects 1 week after the injections; the mean duration of the therapeutic effect was 4.5 months (range 3–9 months). One patient suffered from local hematoma and ecchymosis that did not require medical care. Another patient complained of difficulty swallowing, which did not require medical treatment and resolved spontaneously within 1 month.

Conclusions: Ultrasound-guided botulinum toxin injections into the parotid and submandibular glands seem to be a safe and effective therapy for the treatment of drooling. Further long-term prospective studies with varying doses are warranted.

Background: Facial rejuvenation using different dermal and sub-dermal injectable compounds is a popular cosmetic procedure which may pose a diagnostic dilemma to the radiologist.

Objectives: To describe the appearance of cosmetic facial fillers on PET-CT.

Methods: All PET-CT exams performed between January 2015 and May 2017 in which findings suggestive of prior facial filler procedures was evident and where anamnestic confirmation with the patient was possible were reviewed.

Results: We describe five females who had undergone facial filler procedures leading to calcifications around the mouth and nasolabial triangle.

Conclusions: Familiarity with the appearance of such cosmetic procedures on PET-CT is of paramount importance in order to avoid misinterpretation of the findings leading to unnecessary apprehension and work-up.

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: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular medications. Bevacizumab is mostly used in this group of medications.

Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.

Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30–70 mmHg, 3–30 days after injection.

Results: Mean IOP was 42.6 mmHg (range 30–70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3–13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.

 Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments. 

Background: Intraarticular injections for the local treatment of osteoarthritis are widely used in the office or hospital setting. Septic arthritis is a potential catastrophic complication of intraarticular injection, as bacterial arthritis of any cause is associated with up to 15% mortality and residual impairment of joint function in up to 50% of survivors. There is lack of evidence regarding the precautions that should be taken to avoid such a complication, as well as how often it is encountered.

Objectives: To report our experience with the clinical presentation, diagnosis and treatment of knee septic arthritis following intraarticular injections. 

Methods: We followed six patients who were admitted to the hospital and underwent surgery for the treatment of pyogenic arthritis following injection to the knee joint in outpatient clinics.

Results: All but one patient were over 70 years old with comorbidities. Three patients were injected with steroid preparations and three with hyaluronic acid several days before admission. In all six patients the infection was treated surgically and three of them had undergone more than one operation during their hospitalization. Four of the six patients were treated by means of an open arthrotomy and synovectomy, and the other two were treated successfully with arthroscopic lavage and synovectomy. One patient underwent an above-knee amputation due to septic shock and died after several days.

Conclusions: Despite the rarity of this complication, surgeons must be aware of the possibility of pyogenic arthritis when administering injections, especially in elderly patients with serious underlying medical conditions.