Israel Medical Association Journal

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: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma.

Objectives: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis.  

Methods: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age.

Results: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy.

Conclusions: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: The number of investigative esophagogastroduodenoscopies (EGD) in children has increased over several decades, despite their unclear diagnostic yields.

Objectives: To evaluate the indications for performing EGD, their diagnostic yields, and consequences on pediatric patient management.

Methods: A retrospective chart review was performed of consecutive pediatric patients aged 0–18 years, who underwent EGD between January and August 2014.

Results: During the study period, 547 EGD were performed on 478 children. The most frequent indications were suspected celiac disease, chronic non-specific abdominal pain, persistent Helicobacter pylori infection, and gastrointestinal hemorrhage. The yield of the diagnostic EGD was 59.2%, and the most common new diagnoses were celiac disease (28%), Helicobacter pylori-positive gastritis (16.5%), and Crohn’s disease (5.4%). Of the patients with documented follow-up, 74.1% reported improved symptoms. Procedures performed for chronic unexplained abdominal pain had significantly lower yields (26.2%) and only 39.3% improved at follow-up.

Conclusions: Our findings suggest a general high diagnostic yield for EGD in pediatric patients, stemming mainly from patients in whom a specific condition was suspected a priori. However, the role of the procedure in the diagnosis and management of non-specific gastrointestinal complaints was minor suggesting that EGD may be superfluous for some of these patients.

Background: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited.

Objectives: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function.

Methods: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250–500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids.

Results: Polyp tissue viability was retained for 2–3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production.

Conclusions: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

Background: Implant-related spinal infections are a surgical complication associated with high morbidity. Due to infection, hardware removal may be necessary, which could lead to pseudarthrosis and the loss of stability and alignment.

Objectives: To evaluate the accuracy and diagnostic value of ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT) in the workup of patients with suspected implant-related infections of the spine and to assess the clinical impact of PET/CT results on the management of these infections.

Methods: The study included nine consecutive patients with a history of spinal surgery who underwent PET/CT for evaluation of suspected spinal implant related infection. All imaging studies were performed between January 2011 and December 2013. All ¹⁸F-FDG PET/CT scans were performed on an 8 slice PET/CT following an ¹⁸F-FDG injection. Images were scored both visually and semi-quantitatively by a radiology expert. Results were compared to additional imaging studies when available, which were correlated to clinical and bacteriological findings allowing calculation of sensitivity, specificity and accuracy.

Results: Among the patients, five experienced hardware-related spinal infection. ¹⁸F-FDG PET/CT sensitivity was 80%, specificity 100%, and accuracy 88.9%. One scan produced a false negative; however, a second PET/CT scan revealed an infection.

Conclusions: PET/CT was found to be valuable for the diagnosis of postoperative hardware-related spinal infection, especially when other imaging modalities were uninformative or inconclusive. As such, PET/CT could be useful for management of infection treatment.

Background: Gender differences in adolescent idiopathic scoliosis (AIS) have been documented in curve progression, response to bracing, and outcomes of surgical treatment. However, limited information is available about the relation between gender and scoliosis curve patterns and radiographical characteristics.

Objectives: To evaluate the effect of gender on curve pattern and compare clinical and radiographical characteristics between male and female patients with AIS.

Methods: We conducted a retrospective review of prospectively collected data that compared clinical and radiographical characteristics between male and female surgical candidates. Demographic and clinical data including age at presentation, gender, family history of scoliosis, brace treatment history, clinical coronal balance, shoulder asymmetry, and hump size were recorded. All patients graded their pain with the use of a visual analogue scale (VAS) on a scale from 0 to 10. Radiographs of the spine were reviewed to determine the type of curve according to the Lenke classification, Cobb angle, thoracic kyphosis angle, and the Risser sign. Radiologic coronal balance was recorded. Curve flexibility was determined by measuring the thoracic and lumbar curves magnitude on side bending radiographs

Results: The study included 163 patients with AIS including 35 males and 128 females patients. Although a trend toward more flexible major thoracic curves in females was noticed, there was no statistically significant difference between the 2 groups.

Conclusions: In this study we were not able to demonstrate any clinical nor radiological statistical differences between male and female patients who are candidate for surgical treatment.

Background: Frequent chronic obstructive pulmonary disease (COPD) exacerbators are at a higher risk of adverse health outcomes when compared to infrequent exacerbators. A COPD frequent exacerbator phenotype and its definition has been reported. Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease. The Hp 2-2 phenotype has been found to have bacteriostatic properties, while the Hp 1-1 phenotype was found to be associated with infections.

Objectives: To determine the correlation in haptoglobin phenotypes and the frequent exacerbator status compared to COPD non-exacerbators.

Methods: Inclusion criteria included previous diagnosis of COPD and presence of at least two documented exacerbations of COPD in the previous 12 months (frequent exacerbator group) or absence of such exacerbations in the previous 24 months (non-exacerbator group). Descriptive data was analyzed using Fisher's exact test and the nonparametric Kruskal–Wallis test. Multivariate logistic regression analysis was performed.

Results: The multivariate logistic regression yielded a model in which haptoglobin phenotype did not have a statistically significant association with frequent exacerbator status. Smoking status was found to be negatively related with the frequent exacerbator status (odds ratio [OR] 0.240, 95% confidence interval (95%CI) 0.068–0.843, P = 0.03). Number of pack-years was negatively related to being a frequent exacerbator (OR 0.979, 95%CI 0.962–0.996, P = 0.02).

Conclusions: We found no relationship between haptoglobin polymorphism and frequent exacerbator status. However, frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years and a negative correlation with current smoking status.

Background: Adverse drug events (ADEs) are a major cause of morbidity and mortality worldwide. Hence, identifying and monitoring ADEs is of utmost importance. The Trigger Tool introduced by the Institute of Healthcare Improvement in the United States has been used in various countries worldwide, but has yet to be validated in Israel.

Objective: To validate the international Trigger Tool in Israel and to compare the results with those generated in various countries.

Methods: A retrospective descriptive correlative analysis surveying four general hospitals in Israel from different geographical regions was conducted. Patient medical charts (n=960) were screened for 17 established triggers and confirmed for the presence of an ADE. Trigger incidence was compared to the actual ADE rate. Further comparison among countries was conducted using published literature describing Trigger Tool validation in various countries.

Results: A total of 421 triggers in 279 hospitalizations were identified, of which 75 ADEs in 72 hospitalizations (7.5%) were confirmed. In addition, two ADEs were identified by chart review only. Mean positive predictive value was 17.81% and overall sensitivity was 97%. We found 1.54 ADEs for every 100 hospitalization days, 7.8 ADEs per 100 admissions, and 1.81 ADEs for every 1000 doses of medication. Of the 77 ADEs identified, 22.7% were defined as preventable.

Conclusions: Our results support the Trigger Tool validity in Israel as a standardized method. Further studies should evaluate between hospital and region differences in ADE rate, in particular for the preventable events.

Background: Leukoplakia of the vocal cords may represent a pre-cancerous lesion of the larynx. The management of cases of recurrent leukoplakia with pathologically proven dysplasia is still controversial.

Objectives: To present a series of patients with recurrent vocal cord leukoplakia and to examine their malignant transformation rate in relation to the clinical characteristics, risk factors, and histological findings.

Methods: A retrospective cohort study was conducted between 1999 and 2017. The study comprised 52 patients with recurrent leukoplakia of the vocal cords who required ≥ 2 direct laryngeal procedures within a minimum of 3 months between each procedure. Malignant transformation rate over follow-up period, risk factors for malignant transformation, and interval to develop laryngeal squamous cell carcinoma were investigated.

Results: All patients presented with hoarseness. An average of three procedures per patient was performed (range 2–13). Ten male patients (19.2%) developed squamous cell carcinoma. Of these, four with severe dysplasia developed SCC within 19 months of the first direct laryngoscopy. In the six other patients, SCC developed within an average of 3.7 years. The follow-up period ranged from 9–253 months (mean 109 months). Heavy smoking and severe dysplasia in the first biopsy were found to be significant risk factors for developing squamous cell carcinoma, as was male gender.

Conclusions: We showed an increased malignant transformation rate in recurrent leukoplakia cases among heavy smokers and male patients. In addition, severe dysplasia at initial diagnosis was a risk factor for SCC development. Close follow-up of patients with recurrent leukoplakia is warranted.

Background: When a patient arrives at the emergency department (ED) presenting with symptoms of acute decompensated heart failure (ADHF), it is possible to reach a definitive diagnosis through many different venues, including medical history, physical examination, echocardiography, chest X-ray, and B-type natriuretic peptide (BNP) levels. Point-of-care ultrasound (POCUS) has become a mainstream tool for diagnosis and treatment in the field of emergency medicine, as well as in various other departments in the hospital setting. Currently, the main methods of diagnosis of ADHF using POCUS are pleural B-lines and inferior vena cava (IVC) width and respiratory variation.

Objectives: To examine the potential use and benefits of bedside ultrasound of the jugular veins in the evaluation of dyspneic patients for identification of ADHF.

Methods: A blood BNP level was drawn from each participant at time of recruitment. The area and size of the internal jugular vein (IJV) during inspiration and expiration were examined.

Results: Our results showed that the respiratory area change of the IJVs had a specificity and sensitivity of nearly 70% accuracy rate in indentifying ADHF in our ED.

Conclusions: Ultrasound of the IJV may be a useful tool for the diagnosis of ADHF because it is easy to measure and requires little skill. It is also not affected by patient body habitus.

Background: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. 

Objectives: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. 

Methods: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.

Results: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. 

Conclusions: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.