Israel Medical Association Journal

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: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia.

Objectives: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages.

Methods: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia.

Results: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05).

Conclusions: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Background: Door-to-balloon time (DTBT) ≤ 90 minutes has become an important quality indicator in the management of ST-elevation myocardial infarction (STEMI). We identified three specific problems in the course from arrival of STEMI patients at our emergency department to initiation of balloon inflation and determined an intervention comprised of specific administrative and professional steps. The focus of the intervention was on triage within the emergency department (ED) and on increasing the efficiency and accuracy of electrocardiography interpretation.

Objectives: To examine whether our intervention reduced the proportion of patients with DTBT > 90 minutes.

Methods: We compared DTBT of patients admitted to the ED with STEMI during the year preceding and the year following implementation of the intervention.

Results: Demographic and clinical characteristics at presentation to the ED were similar for patients admitted to the ED in the year preceding and the year following intervention. The year preceding intervention, DTBT was > 90 minutes for 19/78 patients (24%). The year after intervention, DTBT was > 90 minutes for 17/102 patients (17%). For both years, the median DTBT was 1 hour. Patients with DTBT > 90 minutes tended to be older and more often female. Diagnoses in the ED were similar between those with DTBT ≤ 90 minutes and > 90 minutes. In-hospital mortality was 17% (13/78) and 14% (14/102) for the respective time periods.

Conclusions: An intervention specifically designed to address problems identified at one medical center was shown to decrease the proportion of patients with DTBT > 90 minutes.

Background: Management of patients with hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is evolving worldwide. Evaluating the Israeli experience may provide valuable insights.

Objectives: To compare demographics and icatibant treatment patterns and outcomes in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey (IOS) in Israel with those in other countries.

Methods: The IOS is an ongoing observational study that prospectively monitors real-world icatibant safety/tolerability and treatment outcomes.

Results: By July 2016, 58 patients from Israel and 594 patients from other countries were enrolled. Median age at diagnosis (16.7 vs. 21.3 years, P = 0.036) and median delay between symptom onset and diagnosis (0.8 vs. 6.6 years, P = 0.025) were lower in Israel compared with other countries, respectively. Differences in attack severity were not significant (P = 0.156); however, during follow-up, Israeli patients were less likely to miss > 7 days of work/school due to C1-INH-HAE-related complications (P = 0.007). A trend was also shown in Israel for earlier time to treatment (median 0.5 vs. 1.3 hours, P = 0.076), attack duration was shorter (median 5.0 vs. 9.0 hours, P = 0.026), and patients more often self-administered icatibant (97.2% vs. 87.5%, P = 0.003), respectively. However, Israeli patients were less likely to treat attacks (P = 0.036). Whereas patients in Israel reported exclusive use of danazol for long-term prophylaxis, those in other countries used various agents, including C1-INH.

Conclusions: Recognition of C1-INH-HAE and timeliness of icatibant treatment appear more favorable, and attack duration shorter, in Israel compared with other countries.

Background: Warm compresses are widely touted as an effective treatment for ocular surface disorders. Black tea compresses are a common household remedy, although there is no evidence in the medical literature proving their effect and their use may lead to harmful side effects. 

Objectives: To describe a case in which the application of black tea to an eye with a corneal epithelial defect led to anterior stromal discoloration; evaluate the prevalence of hot tea compress use; and analyze, in vitro, the discoloring effect of tea compresses on a model of a porcine eye.

Methods: We assessed the prevalence of hot tea compresses in our community and explored the effect of warm tea compresses on the cornea when the corneal epithelium’s integrity is disrupted. An in vitro experiment in which warm compresses were applied to 18 fresh porcine eyes was performed. In half the eyes a corneal epithelial defect was created and in the other half the epithelium was intact. Both groups were divided into subgroups of three eyes each and treated experimentally with warm black tea compresses, pure water, or chamomile tea compresses. We also performed a study in patients with a history of tea compress use. 

Results: Brown discoloration of the anterior stroma appeared only in the porcine corneas that had an epithelial defect and were treated with black tea compresses. No other eyes from any group showed discoloration. Of the patients included in our survey, approximately 50% had applied some sort of tea ingredient as a solid compressor or as the hot liquid.

Conclusions: An intact corneal epithelium serves as an effective barrier against tea-stain discoloration. Only when this layer is disrupted does the damage occur. Therefore, direct application of black tea (Camellia sinensis) to a cornea with an epithelial defect should be avoided.

 

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the “real-life” safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3–4 months. Adverse events were obtained from patients’ medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1–7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Background: Chronic urticaria (CU) is a common disabling disorder. The CU-Q2oL (Chronic Urticaria Quality of Life Questionnaire) is a specific questionnaire for evaluating quality of life in CU patients. It consists of 23 items divided into six quality-of-life dimensions. It was initially developed in Italy and later validated in other countries.

Objectives: To validate and adapt the CU-Q2oL to the Hebrew language in order to make it suitable for use in Israel. 

Methods: The CU-Q2oL questionnaire was translated to Hebrew. A group of 119 CU patients were asked to complete this version, in addition to the Dermatology Life Quality Index (DLQI) and Urticaria Activity Score (UAS) questionnaires. A factorial analysis was performed to identify CU-Q2oL subscales, internal consistency and convergent validity assessment, as well as factors determining quality-of-life scores.

Results: The factor analysis identified six scales of the Israeli CU-Q2oL: (i) sleep and concentration, (ii) function and mental status, (iii) embarrassment and clothing limitations, (iv) itching, (v) eating behavior and medication side effects, and (vi) swelling, which accounted for 77% of the data variance. Five scales showed good internal consistency over 0.81. The mean ± SD score of CU-Q2oL in our patients with CIU was 41 ± 21.7. We found a strong positive correlation between the overall scores of CU-Q2oL and DLQI questionnaires (r = 0.8, P < 0.01). Additionally, we found a positive correlation between UAS and both CU-Q2oL and DLQI (r = 0.62, P < 0.01, and r = 0.53, P < 0.01, respectively). 

Conclusions: This study demonstrates that the Israeli CU-Q2oL questionnaire is suitable for both clinical use and research in Israel.