Israel Medical Association Journal

Background: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED).

Objectives: To assess the association between CIEDs and severity of COVID-19 infection.

Methods: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed.

Results: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED.

Conclusions: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although,CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

This mini review includes two case descriptions. It introduces the use of chicken egg yolk antibody (IgY) solutions in the prevention and cure of viral and bacterial infections. Application for the protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rotavirus, and influenza viruses, as well as for the eradication of Pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. This approach is a fast, reliable, safe, and tested method for producing molecular shield and protection against emerging pathogens and epidemics. In the current pandemic situation caused by coronavirus disease-2019 (COVID-19), this method of passive immunization could be applied for rapid protection against modifiable agents. The specific IgY antibodies start to accumulate into egg yolks about 3 weeks after the immunization of the chicken. The product can be collected safely, as the antigen is not found in the eggs. This method for microbial safety uses natural means and commonly used food substances, which have been tested and could be produced for both blocking epidemics and applying personalized medicine

Background: Opposition to neonatal Hepatitis B vaccination is a growing trend in Israel.

Objectives: To assess the sociodemographic factors and attitudes associated with non-vaccination of term singleton newborns.

Methods: This prospective, pair-matched, controlled trial was conducted in a tertiary university-affiliated hospital. Data on maternal sociodemographic parameters, delivery, and infant care practices were gathered. Knowledge and references of Hepatitis B virus (HBV) vaccination, vaccination schedule, and health government policies were assessed. A follow-up telephone survey was completed at the age of 7 weeks postpartum regarding vaccine catch-up rate.

Results: Mothers in the study group were mostly Jewish white middle class married multiparous women with some higher education. Hepatitis B serology was not tested in most. Higher rates of rooming-in and exclusive breastfeeding were observed. Knowledge about HBV was stated, multiple sources of information were significantly associated with newborn non-vaccination. Many objected to the timing of the vaccine and its necessity. Multiple medical encounters are viewed as missed opportunities.

Conclusions: Multiple sources of vaccine information are associated with non-vaccination. Medical encounters prior and post-delivery should be used for vaccination education and may improve vaccination coverage.

Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed.

Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential.

Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases.

Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10).

Conclusion: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease of the peripheral nervous system with a typical presentation of acute paralysis and hyporeflexia. Intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are treatments that have proven to expedite recuperation and recovery of motor function.

Objectives: To describe our experience at one tertiary medical center treating GBS with IVIG and to compare the efficacy of IVIG as the sole treatment versus combined therapy of IVIG and plasma exchange.

Methods: We reviewed the records of all patients diagnosed with GBS and treated with IVIG at the Sheba Medical Center from 2007 to 2015 and collected data on patient demographics, disease onset and presentation, and treatments delivered. The motor disability grading scale (MDGS) was used to evaluate the motor function of each patient through the various stages of the disease and following therapy.

Results: MDGS improvement from admission until discharge was statistically significant (P < 0.001), as was the regainment of motor functions at 3 and 12 months follow-up compared to the status during the nadir of the disease. The effectiveness of second-line treatment with IVIG following PLEX failure and vice versa was not statistically significant (P > 0.15).

Conclusions: The majority of patients included in this study experienced a significant and rapid improvement of GBS following treatment with IVIG. Combined therapy of PLEX and IVIG was not proven to be effective in patients who encountered a failure of the first-line treatment.

Background: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease with poor prognosis despite intensive therapy.

Objectives: To discuss the ideal therapy of EBV-associated HLH for adults.

Methods: We retrospectively studied 23 adult patients with EBV-associated HLH at our institution between January 2000 and June 2015. The clinical characteristics, treatment, and prognosis of adult EBV-associated HLH were analyzed. The median age was 38 years (range 18–72).

Results: All patients were found to have high fever, thrombocytopenia, abnormal liver function, elevated ferritin, and lactate dehydrogenase. Leukopenia, anemia, coagulopathy, hypofibrinogenemia, and splenomegaly were found in more than 80% of patients. Ten patients were treated with HLH-2004 protocol. Eventually, 95.7% of patients died of EBV-associated HLH. Non-HLH-2004 treatment and bone marrow suppression may predict early relapse independently, and the poor performance status and high lactate dehydrogenase level can be poor prognostic factors. It was also validated in comprehensive analysis of published articles.

Conclusions: Adult EBV-associated HLH occurs most often in people of Asian descent who are older than 35 years. These patients had a disappointing outcome despite intensive treatment, especially with high lactate dehydrogenase levels, poor performance status, and bone marrow suppression. HLH-2004 protocol has shown a glimmer of hope in the adult populations.

Background: The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population.

Objectives: To analyze the seroprevalence of EBV infection in different population groups in Croatia.

Methods: During a 2 year period (2015–2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity.

Results: The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age < 9 years to 98.3% in 30–39 year olds, and remained stable thereafter (P < 0.001). The IgG seroprevalence differed significantly among groups: 68.1% in children/adolescents and 95.9% in adults; multiple sclerosis (100%), hemodialysis patients (97.7%), heart transplant recipients (93.8%), hematological malignancies (91.2%), and Crohn’s disease (88.5%), P < 0.001. IgM antibodies were detected in 9% of participants. Using IgG avidity, recent primary EBV infection was documented in 83.8% of IgM-positive subjects < 9 years old, 69.2% age 10–19, 33.3% age 20–29, and 3.6–4.2% > 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic regression showed that age is associated with EBV IgG seropositivity.

Conclusions: EBV is widespread in the Croatian population. Older age appears to be the main risk factor for EBV seropositivity.

Background: During 2013–2014 Israel experienced a continuous circulation of wild poliovirus type 1 (WPV1) but with no clinical cases. WPV1 circulation was gradually terminated following a national vaccination campaign of bivalent oral poliovirus vaccine (bOPV) for 943,587 children < 10 years. Four cases of children with neurological manifestations that appeared following bOPV vaccinations were reported during the campaign: three of Guillain-Barré syndrome (GBS) and one of acute disseminated encephalomyelitis (ADEM). 

Objectives: To present an analysis of these cases, the rapid response and the transparent publication of the results of this analysis. 

Methods: The clinical, laboratory and epidemiological data of these four patients were available during the analysis. In addition, data regarding the incidence of GBS and ADEM during previous years, and reported cases of acute flaccid paralysis (AFP) and the incidence of Campylobacter jejuni enteritis were collected from the Epidemiology Department of the Israel Ministry of Health.

Results: The incidence of GBS among bOPV-vaccinated children was not higher than among bOPV-unvaccinated children. For all the cases reviewed the "incubation period" from vaccination to the event was longer than expected and other more plausible causes for the neurologic manifestations were found. There is no evidence in the literature of a causal relationship between bOPV and ADEM. 

Conclusions: There was no association between the bOPV vaccine and the reported neurological manifestations. We believe that our experience may assist other public health professionals when confronting a similar problem of alleged side effects during a mass medical intervention.