Israel Medical Association Journal

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk after percutaneous coronary intervention (PCI).

Objectives: To compare the clinical outcomes within 30 days, one year, and five years of undergoing PCI.

Methods: We conducted a retrospective cohort study of adult patients with IBD who underwent PCI in a tertiary care center from January 2009 to December 2019.

Results: We included 44 patients, 26 with Crohn’s disease (CD) and 18 with ulcerative colitis (UC), who underwent PCI. Patients with CD underwent PCI at a younger age compared to UC (57.8 vs. 68.9 years, P < 0.001) and were more likely to be male (88.46% of CD vs. 61.1% of UC, P < 0.03). CD patients had a higher rate of non-steroidal treatment compared to UC patients (50% vs. 5.56%, P < 0.001). Acute coronary syndromes (ACS) and/or the need for revascularization (e.g., PCI) were the most common clinical events to occur following PCI, in both groups. Of patients who experienced ACS and/or unplanned revascularization within 5 years, 25% of UC vs. 40% of CD had target lesion failure (TLF) due to in-stent restenosis and 10% of CD had TLF due to stent thrombosis.

Conclusions: We observed higher rates of TLF in IBD patients compared to the general population as well as differences in clinical outcomes between UC and CD patients. A better understanding of the prognostic factors and pathophysiology of these differences may have clinical importance in tailoring the appropriate treatment or type of revascularization for this high-risk group.

A rise in the incidence of chronic health conditions, notably heart failure, is expected due to demographic shifts. Such an increase places an onerous burden on healthcare infrastructures, with recurring hospital admissions and heightened mortality rates being prominent factors. Efficient chronic disease management hinges on regular ambulatory care and preemptive action. The application of intelligent computational models is showing promise as a key resource in the ongoing management of chronic diseases, particularly in forecasting disease trajectory and informing timely interventions. In this review, we explored a pioneering intelligent computational model by Diagnostic Robotics, an Israeli start-up company. This model uses data sourced from insurance claims to forecast the progression of heart failure. The goal of the model is to identify individuals at increased risk for heart failure, thus enabling interventions to be initiated early, mitigating the risk of disease worsening, and relieving the pressure on healthcare facilities, which will result in economic efficiencies.

Over the last decade the use of artificial intelligence (AI) has reformed academic research. While clinical diagnosis of psoriasis and psoriatic arthritis is largely straightforward, the determining factors of a clinical response to therapy, and specifically to biologic agents, have not yet been found. AI may meaningfully impact attempts to unravel the prognostic factors that affect response to therapy, assist experimental techniques being used to investigate immune cell populations, examine whether these populations are associated with treatment responses, and incorporate immunophenotype data in prediction models. The aim of this mini review was to present the current state of the AI-mediated attempts in the field. We executed a Medline search in October 2023. Selection and presentation of studies were conducted following the principles of a narrative–review design. We present data regarding the impact AI can have on the management of psoriatic disease by predicting responses utilizing clinical or biological parameters. We also reviewed the ways AI has been implemented to assist development of models that revolutionize the investigation of peripheral immune cell subsets that can be used as biomarkers of response to biologic treatment. Last, we discussed future perspectives and ethical considerations regarding the use of machine learning models in the management of immune-mediated diseases.

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.