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: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant.

Objectives: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma

Methods: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy.

Results: Fourteen patients presented with ICH (6.8%, 3.8–11.1%) and three (1.5%, 0.3–4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0–2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8–98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7–88.3) of the cohort.

Conclusions: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

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.

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: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection in immunocompromised patients. Clusters of PJP, especially among organ transplant recipients in clinic settings were described. Data regarding nosocomial PJP infection among inpatients are limited.

Objectives: To assess the magnitude and characteristics of inpatient healthcare-associated PJP infection (HCA-PJP) in HIV-negative patients.

Methods: A retrospective chart review of hospitalized PJP patients was performed to identify HCA-PJP. The study was performed at six medical centers in Israel from 2006 to 2016. HCA-PJP was defined as cases of hospital-onset or those with documented contact with a PJP patient. We reviewed and cross-matched temporal and spatial co-locations of patients. Clinical laboratory characteristics and outcomes were compared.

Results: Seventy-six cases of PJP were identified. Median age was 63.7 years; 64% men; 44% hematological malignancies; 18% inflammatory diseases; and 61% steroid usage. Thirty-two patients (42%) were defined as HCA-PJP: 18/32 (23.6%) were hospitalized at onset and 14/32 (18.4%) had a previous encounter with a PJP patient. Time from onset of symptoms to diagnosis was shorter in HCA-PJP vs. community-PJP (3.25 vs. 11.23 days, P = 0.009). In multivariate analysis, dyspnea at presentation (odds ratio [OR] 16.79, 95% confidence interval [95%CI] 1.78–157.95) and a tendency toward higher rate of ventilator support (72% vs. 52%, P = 0.07, OR 5.18, 95%CI 0.7–30.3) were independently associated with HCA-PJP, implying abrupt disease progression in HCA-PJP.

Conclusion: HCA-PJP was common. A high level of suspicion for PJP among selected patients with nosocomial respiratory infection is warranted. Isolation of PJP patients should be considered

Coronavirus disease-2019 (COVID‐19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series

Background: Point shear-wave elastography (pSWE) is a new method to assess the degree of liver fibrosis. It has been shown to be effective in detecting stiffness in viral hepatitis.

Objectives: To determine the feasibility of pSWE for assessing liver stiffness and fibrosis in liver diseases of different etiologies.

Methods: This prospective single-center study included a population of adult patients with chronic liver diseases from different etiologies, who were scheduled for liver biopsy, and a control group of healthy adults who prospectively underwent pSWE. Ten consecutive pSWE measurements of the liver were performed using a Philips iU22 ultrasound system. Stiffness degree was compared to liver biopsy results. Fibrosis degree was staged according to METAVIR scoring system.

Results: The study group was comprised of 202 patients who underwent liver biopsy and pSWE test and a control group consisting of 14 healthy adults who underwent pSWE for validation. In the study group, the median stiffness was 5.35 ± 3.37 kilopascal (kPa). The median stiffness for F0–1, F2, F3, and F4 as determined by liver biopsy results were 4.9 kPa, 5.4 kPa, 5.7 kPa, and 8 kPa, respectively. The median stiffness in the control group was 3.7 ± 0.6 kPa. Subgroup analyses were conducted for viral hepatitis vs. non-viral hepatitis and steatohepatitis vs. non-steatohepatitis groups.

Conclusions: pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values

Background: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known.

Objectives: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI.

Methods: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF.

Results: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0–3.59, P = 0.04) for patients in the third CRPv tertile.

Conclusion: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.