Israel Medical Association Journal

Background: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound.

Objectives: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals.

Methods: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment.

Results: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1.

Conclusions: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings

Background: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue.

Objectives: To report three unique cases of GPA presenting with tumor-like lesions in various organs.

Methods: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass.

Results: The patients were treated successfully with rituximab.

Conclusions: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener’s granulomatosis

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Background: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair.

Objectives: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects.

Methods: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture.

Results: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group.

Conclusions: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.

Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.

Background: With diagnostic imaging, such as a duplex of the carotid arteries, finding of stenosis and atherosclerotic plaque and consequent end arterectomy may be important for decreasing the danger of developing cerebrovascular accident after transient ischemic attack (TIA).

Objectives: To measure performance rates of duplex of carotid arteries within 72 hours of TIA diagnosis.

Methods: The denominator included all patients who were admitted to emergency departments because of TIA, and the numerator included those who underwent duplex within 72 hours of admission. Inclusion criteria included all patients older than 18 years who were admitted because of TIA according to the ICD9 codes.

Results: Measuring this indicator started in 2015 with 5504 patients and a 58% success rate. The figures for the years 2016, 2017, and 2018 were 5309, 5447, and 5278 patients with success rates of 73%, 79%, and 83%, respectively. Six of 26 hospitals (23.0%) reached the target of 80% in 2018. From 2015 to 2018 a total of 21,538 patients were admitted to emergency departments in Israel and diagnosed with TIA. Of these, 15,722 (72.9%) underwent duplex within 72 hours. The mortality rate within 30 days from diagnosis was 0.81% in patients who performed duplex within 72 hours of diagnosis and 2.37% in patients who did not, odds ratio 2.676, 95% confidence interval 2.051–3.492, P < 0.0001. These results indicate a statistically significant decrease of 65.82%.

Conclusions: A significant decrease in mortality was noted in patients with a new diagnosis of TIA who underwent duplex within 72 hours of diagnosis

Background: The coronavirus disease-2019 (COVID-19) outbreak had an effect on healthcare.

Objectives: To evaluate the presentation and management of patients with acute appendicitis.

Methods: A retrospective study was conducted of all patients presenting with acute appendicitis to the emergency department of a large tertiary center during March and April 2020. Clinical features, diagnostic workup, and management were compared.

Results: Seventy-four patients presented with acute appendicitis during the pandemic compared to 60 patients during the same time the year before. There were no significant differences in patient demographics: age (P = 0.65), gender (P = 0.73), smoking status (P = 0.48). During COVID-19 patients were more likely to complain of right lower quadrant pain (100% vs. 78.3%, P < 0.01). Rates of surgical treatment was similar (83.8% vs. 81.7%, P = 1); mean operative time was longer during COVID-19 (63 ± 23 vs. 52 ± 26 minutes, P = 0.03). There were no significant differences in intra-operative findings including the presence of appendiceal perforation (16.3% vs. 14.5%, P = 0.8), abscess (6.1% vs. 9.7%, P = 0.73), or involvement of cecum or terminal ileum (14.28% vs. 19.63%, P = 1). Postoperative treatment with antibiotics was more prevalent during COVID-19 (37.1% vs. 18%, P = 0.04). Length of stay (1.82 ± 2.04 vs. 2.74 ± 4.68, P = 0.2) and readmission rates (6% vs. 11.3%, P =0.51) were similar.

Conclusion: The COVID-19 pandemic did not significantly affect the presentation, clinical course, management, and outcomes of patients presenting with acute appendicitis.

This focus article is a theoretical reflection on the ethics of allocating respirators to patients in circumstances of shortage, especially during the coronavirus disease-2019 (COVID-19) outbreak in Israel. In this article, respirators are placeholders for similar life-saving modalities in short supply, such as extracorporeal membrane oxygenation machines and intensive care unit beds.

In the article, I propose a system of triage for circumstances of scarcity of respirators. The system separates the hopeless from the curable, granting every treatable person a real chance of cure. The scarcity situation eliminates excesses of medicine, and then allocates respirators by a single scale, combining an evidence-based scoring system with risk-proportionate lottery.

The triage proposed embodies continuity and consistency with the healthcare practices in ordinary times. Yet, I suggest two regulatory modifications: one in relation to expediting review of novel and makeshift solutions and the second in relation to mandatory retrospective research on all relevant medical data and standard (as opposed to experimental) interventions that are influenced by the triage

Background: Management of acquired laryngotracheal stenosis (LTS) is challenging and often requires recurrent procedures.

Objectives: To compare the efficacy and safety of balloon dilatation (BD) versus rigid dilatation (RD) in the treatment of LTS.

Methods: A retrospective study of patients undergoing endoscopic intervention for LTS was performed.

Results: The study included 69 balloon (BD) and 48 rigid dilations (RD). Most cases were grade 3 Cotton-Meyer stenosis. Mean time interval to recurrence after BD and RD were 27.9 and 19.6 weeks, respectively. Remission of over 8 weeks was achieved in 71% of BD compared to 31.2% of RD (P < 0.05). In the BD group, dilatation of subglottic stenosis showed higher rates of remission of over 8 weeks compared to upper and mid-tracheal stenosis (92% vs. 62% and 20%, respectively, P < 0.05). Complications were encountered in 4.2% of RD and 2.9% of BD.

Conclusions: BD and RD are effective and safe procedures. Overall, BD achieved slightly better long-term results compared to RD

Background: The cold season seems to be a trigger for atrial fibrillation (AF). Some reports are controversial and demonstrate variability according to the climatic characteristics in different regions.

Objective: To analyze whether meteorological factors contribute to seasonal variation of exacerbation of AF diagnosed in patients referred to the emergency department (ED) of our hospital.

Methods: We retrospectively reviewed medical data of consecutive patients admitted to the ED with symptomatic acute onset AF from 1 January 2016 to 31 December 2018. We recorded the mean monthly outdoor temperature, barometric pressure, and relative humidity during the study period.

Results: During the study period, 1492 episodes of AF were recorded. New onset AF were 639 (42.8%) and paroxysmal atrial fibrillation (PAF) were 853 (57.2%) (P = 0.03). The number of overall admission of AF episodes was not distributed uniformly through the year. Incidence of AF episodes peaked during December and was lowest in June (P = 0.049). Of 696 episodes (46.6 %) the patients were hospitalized and for 796 (53.4%) the patients were discharged (0.01). The number of hospitalizations was not distributed uniformly through the year (P = 0.049). The highest number of hospitalizations happened in December and the lowest in May. Outdoor temperature and barometric pressure (but not relative humidity) may mediate a monthly fluctuation in AF episodes with highest number of ED visits in December and the lowest in June.

Conclusions: Meteorological conditions influence exacerbation of AF episodes and hospitalization. Outdoor temperature and barometric pressure may mediate a monthly fluctuation in AF