Israel Medical Association Journal

Background: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.

Objectives: To study different triggers for DKA and their effect on outcomes.

Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.

Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35–14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).

Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Background: Although minimally invasive surgery for Crohn’s disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures with an extra-corporeal anastomosis.

Objectives: To evaluate the short- and long-term outcomes of total laparoscopic ileocolic resection with an intracorporeal anastomosis for Crohn’s disease patients.

Methods: We conducted a single-center retrospective review of all patients who underwent primary ileocolic resection for Crohn’s disease between 2010 and 2021. Group A included 34 patients who underwent total laparoscopic ileocolic resection with intracorporeal anastomosis. Group B comprised 144 patients who underwent an open or laparoscopic-assisted procedure.

Results: No differences were noted in operative time (mean 167 minutes vs. 152 minutes, P = 0.122), length of stay (median 6.4 days vs. 7.5 days, P = 0.135), readmission rates (11.8% vs. 13.2%, P = 1), and microscopic involvement of surgical margins (7.7% vs. 18.5%, P = 0.249). Group A had significantly fewer postoperative surgical site infections (2.9% vs. 22.2% respectively, P = 0.013), with no differences in other complications prevalence. After a median follow-up of 46 months, there were similar rates of endoscopic recurrence (47.1% vs. 51.4%, P = 0.72), clinical recurrence (35.3% vs. 47.9%, P = 0.253), and surgical recurrence (2.9% vs. 4.9%, P = 0.722).

Conclusions: Total laparoscopic ileocolic resection with intracorporeal anastomosis for Crohn’s disease is safe and resulted in favorable outcomes in terms of postoperative wound healing. The long-term disease recurrence rates were like those of laparoscopic-assisted and open ileocolic resection.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated condition characterized by fibro-inflammatory lesions with lymphoplasmacytic infiltration. Diagnosis traditionally relies on histopathological findings, including the presence of IgG4+ plasma cells. However, due to challenges in biopsy accessibility, additional measures are needed to facilitate diagnosis.

Objectives: To identify additional parameters for characterizing IgG4-RD patients.

Methods: We compared several circulating factors between a cohort of patients with IgG4-RD disease seen at our hospital between 2017 and 2023 and healthy controls.

Results: Among 16 suspected patients, 13 were confirmed to have IgG4-RD, and 3 were classified as highly likely. Comparison with controls revealed differences in white blood cell count (WBC) (Folf change (FC) 1.46, P < 0.05), plasmablasts (FC 3.76, P< 0.05), plasmablasts CD38 (FC 1.43, P < 0.05), and CD27 (FC 0.66, P = 0.054), thus highlighting potential markers for IgG4-RD diagnosis. Treatments with steroids/rituximab tend to reduce plasmablast (FC 0.6) and IgG4 (FC 0.28) levels and to increase Gal-3 levels.

Conclusions: Levels of plasmablasts are a significant diagnostic feature in IgG4-RD. Healthy individuals have a lower level of plasmablasts. Elevated Gal-3 in serum of patients with IgG4-RD suggests a role in plasmablast activation. CD38/CD27 expression by plasmablasts emerges as a potential marker. Further research on a larger cohort is needed to confirm these findings.

Background: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost.

Objectives: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019.

Methods: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference.

Results: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019.

Conclusions: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism and manifests as a multisystem disease. Most patients present with oropharyngeal malformations, cardiomyopathies, elevated liver enzymes, and hypoglycemia. Treatment with D-galactose has been shown to improve symptoms. Our patient presented with PGM1 deficiency. She conceived spontaneously. Throughout her pregnancies, our patient was monitored by a multidisciplinary team of cardiologists, endocrinologists, and physicians with experience in high-risk pregnancy. She delivered twice by cesarean section. Our case highlights the importance of a multidisciplinary approach and individualized management of prenatal and postpartum care of a patient with a PGM1 deficiency. To the best of our knowledge, there have been no reports about a PGM1-deficient patient who conceived and delivered.

Since the introduction of the international study group (ISG) criteria for the diagnosis of Behçet's disease (BD) in the early 1990s by Yazici and colleagues [1] and the international criteria for BD (ICBD) by Davatchi and colleagues in 2014 [2], great progress has been achieved in the diagnosis of BD with fairly high sensitivity and specificity rates. However, a small, but very challenging and unique minority might not fulfill these criteria, at least at presentation. These patients are most challenging as they may present with life-threatening vascular or neurological manifestations. If the diagnosis BD is delayed, the risk for morbidity and even mortality might be increased. Therefore, we should aim for early diagnosis and prompt treatment.

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.