Israel Medical Association Journal

Background: The coronavirus disease 2019 (COVID-19) pandemic caused significant global turmoil, including changes in social and societal conduct such as lockdowns, social isolation, and extensive regulations. These changes can be major sources of stress. The first wave of the pandemic (April–May 2020) was a time of global uncertainty. We evaluated symptom severity among 29 Israeli children and adolescents with obsessive-compulsive disorder (OCD). Our previous study found that most of these participants did not experience an exacerbation of symptoms.

Objective: To re-evaluate the OCD symptoms of 18 participants from the original group of 29 children and adolescents during three time points: before the pandemic, during the first wave, and 2 years later.

Methods: Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), a functional questionnaire, and the Obsessive-Compulsive Inventory-child version (OCI-CV).

Results: OCS in patients did not change significantly during the three time points. Participants reported minimal changes in their general functioning 2 years after the outbreak of COVID-19 and showed minimal change in OCI-CV scale scores.

Conclusions: Our results indicated clinical stability of OCD symptoms among most of the participants.

Background: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective.

Objectives: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses.

Methods: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose.

Results: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (21² vs. 31⁵ weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048–0.926, P = 0.039).

Conclusions: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Background: Meibomian gland dysfunction (MGD) causes significant patient morbidity as well as economic burden.

Objectives: To evaluate a novel eyelid warming and a neuro-stimulating device that delivers heat via low-level infrared radiation to the eyelids of patients with MGD.

Methods: In this prospective interventional study, patients with MGD were recruited at a single medical center. The main outcome measures included changes in tear break-up time (TBUT), Schirmer’s test, and Ocular Surface Disease Index (OSDI), overall satisfaction, and corneal signs of dry eye. Patients were instructed to use the device twice daily for 5 minutes on each eye for a total of 14 days. Follow-up assessments were performed after the 2-week treatment.

Results: A total of 10 patients were included; mean age was 67 ± 16 years; six males (60%). Changes in pre- vs. post-treatment TBUT (5.0–6.11), OSDI (28.1–23.9), and Schirmer score (8.67–7.11) were not statistically significant. Over a course of 243 treatments, 131 (54%) demonstrated improvement in symptoms, 40% found no change, and 6% experienced worsening of symptoms. General satisfaction was observed overall in 80% of the patients. No adverse events were observed.

Conclusions: In this first study of a novel eyelid warming device, overall subjective satisfaction was reported in 80% of patients. Potential advantages of this user-friendly device include its ability to improve MGD and tear film stability, as well as symptomatic relief, while allowing the user to continue with normal daily functioning while undergoing treatment.

Paraneoplastic syndromes are reported in 8–15% of patients diagnosed with cancer [1]. They are defined as syndromes that occur due to an underlying malignancy, which has yet to be diagnosed, or at the time of the diagnosis and less frequently following the diagnosis of a malignancy. Several mechanisms are involved including autocrine and paracrine mediators, hormones, peptides, cytotoxic lymphocytes, and cytokines [1,2].

The cause of death for Pharaoh Tutankhamun (ca. 1330–1324 BCE) is still unknown despite the advancement in modern paleopathology and the introduction of computed tomography mummy examination and modern molecular pathology, including PCR-based gene analysis. Many speculations regarding his unexpected death have been published, including crush injury, infectious diseases such as malaria, and hereditary disease. We discuss for the first time all these events that could have ultimately caused Tutankhamun's sudden death, particularly sickle cell disease, which can cause osteonecrosis and lead to walking disability, bone deformities, and fragility. Malaria-associated tropical splenomegaly, as an acquired infectious disease, and the crush injury, which represents an acute event, were verified by a left distal femur fracture that contributed to splenic rupture as a major fatal event. We highlight important issues that can provide clinicians and clinical care practitioners with a broad vision while analyzing such cases.

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by restricted airflow, changes of lung tissues, and breathing difficulties [1]. Most patients are treated at home to maintain a stable lifestyle and quality of life [2].

An important feature of COPD is exacerbation, which is an acute worsening of symptoms that can result in decreased pulmonary functions, increased risk of death, and poorer quality of life. The frequency and severity of each exacerbation results in further worsening of pulmonary function [3]. Depression in COPD patients may cause objective impairment in function and decreased adherence to therapeutic interventions [4].

Acute stress disorder is characterized by acute reaction in the first month following exposure to a traumatic event such as threatened death, serious injury, or sexual assault. Symptoms include intrusion, dissociation, negative mood avoidance, and arousal [5]. Stress on a more continuous basis can significantly debilitate a person's emotional and physical wellbeing, lead to depression and weakened immune system, and influence patients with already stressful and progressive conditions such as COPD.

We present a patient previously diagnosed with COPD who experienced an acute terror attack, which was a major and stressful event that caused severe exacerbation of the disease.

Celiac disease (CD) is an immune-based reaction to dietary gluten. CD can present with a diverse array of symptoms. Many CD patients have no symptoms at all. Thus, a great number of atypical cases of CD remain undiagnosed, leading to a risk of long-term complications. Some atypical symptoms of CD such as pregnancy complications, infertility, recurrent abortions, intrauterine growth restriction, preterm delivery, and severe preeclampsia have been investigated in undiagnosed and diagnosed pregnant women with CD. Nutrient deficiency and autoimmune pathogenic mechanisms have been hypothesized to be the explanation of these adverse pregnancy outcomes. Recently, an association between obstetric complications and anti-tissue transglutaminase antibodies titers in women with CD has been reported. While the adverse effects of CD on the reproductive system are well investigated, there are only a few reports in the literature on the effect of pregnancy and puerperium on CD. We reviewed the published literature on the adverse effects and pathophysiology of CD in reproductive disorders and the effect of pregnancy and puerperium on the manifestation of CD.

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Status epilepticus (SE) is a neurological emergency requiring immediate evaluation and management to prevent significant morbidity or mortality. Previously, status epilepticus was defined as a seizure with a duration equal to or greater than 30 minutes or a series of seizures in which the patient does not regain normal mental status between seizures. The Neurocritical Care Society guidelines from 2012 revised the definition to a seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures.

Status epilepticus may be convulsive, non-convulsive, focal motor, or myoclonic, and any can become refractory. Convulsive status epilepticus consists of generalized tonic-clonic movements and mental status impairment. Non-convulsive status epilepticus is defined as seizure activity identified on an electroencephalogram with no accompanying tonic-clonic movements. Focal motor status epilepticus involves the refractory motor activity of a limb or a group of muscles on one side of the body with or without loss of consciousness. Refractory status epilepticus refers to continuing seizures (convulsive or non-convulsive) despite appropriate antiepileptic drugs [1].

Background: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision.

Objectives: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD.

Methods: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity.

Results: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively.

Conclusions: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Recent studies using propensity score matching have clearly indicated that contrast nephropathy following computed tomography occurs in hospitalized patients with advanced chronic kidney disease (eGFR < 30 ml/min/1.73 m²) and that this iatrogenic complication is likely underestimated because of concomitant renal functional recovery, unrelated to the imaging procedure. These findings should be considered regarding contrast-enhanced studies in such patients.

Background: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce.

Objectives: To compare the outcomes of patients with both the Omicron variant and influenza during 2021–2022.

Methods: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality.

Results: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25–0.81).

Conclusions: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Background: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation).

Objectives: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula.

Methods: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded.

Results: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group.

Conclusions: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.