Israel Medical Association Journal

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: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Background: Recurrent tuberculosis (TB) is one of the indices used to assess the effectiveness of the Israeli National TB Programs (NTP).

Objectives: To estimate the incidence of recurrent TB in Israel and to identify the associated risk factors.

Methods: We conducted a retrospective cohort study of all TB patients who were Israeli citizens and diagnosed between 1999 and 2011 with a treatment outcome recorded as “success." We compared those who had recurrent TB with those who did not. In addition, a nested case-control study included all those who had recurrent TB with a random sample from this cohort matched by age, gender, and year of TB diagnosis.

Results: Of 3515 TB patients diagnosed between 1999 and 2011, 37 (1.05%) had recurrent TB during the follow-up period, with an incidence rate of 1.55 cases per 1000 person-years (PY). Male gender [hazard ratio (HR) 3.2, 95% confidence interval (95%CI) 1.4–7.4], human immunodeficiency virus (HIV) infection (HR 3.9, 95%CI 1.5–10.4), positive sputum culture [odds ratios (OR) 2.7, 95%CI 1.1–6.9], and low adherence to anti-TB treatment (OR 3.2, 95%CI 1.0–10.3) were found to be risk factors for recurrent TB.

Conclusions: Male gender, HIV infection, positive sputum culture, and low adherence to anti-TB drugs during the initial TB episode were risk factors for developing recurrent TB.

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Background: Use of the internet and videogames by children and adolescents has risen dramatically over the last decade. Increasing evidence of internet and videogame addiction among children is causing concern due to its harmful physical, emotional and social consequences. There is also emerging evidence for an association between computer and videogame addiction and attention deficit/hyperactivity disorder (ADHD). 

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Background: Clefts of the lip and palate are the most common significant congenital birth anomaly of orofacial region. The condition may vary from a minor easily correctable cleft to a significant functional and cosmetic incapacitation. This is the first epidemiological study of orofacial clefts in the Negev region in Israel.

Objectives: To establish the frequency of cleft lip and palate in the population of the Negev, characterize the demographic features of affected individuals and find possible risk factors, compare the risk in two major population groups: Bedouin and Jewish in a well-defined geographic area, and determine whether there is a change over time in the birth of babies with facial clefts.

Methods: We conducted a retrospective survey of the Soroka Medical Center archives. The sample population comprised all 131,218 babies born at Soroka during the 11 year period 1 January 1996 to 31 December 2006. Statistical tests used Pearson's chi-square test, Student’s t-test and Spearman's correlation coefficient test according to the type of parameter tested.

Results: During the study period 140 babies were born with orofacial cleft. The overall incidence of cleft lip and palate was 1.067/1000. The incidence of facial clefts was 1.54/1000 among Bedouins and 0.48/1000 among Jews (P < 0.001). Cleft palate was significantly more frequent in female than male babies (P = 0.002). Over the study years we found a significant decrease in the incidence of facial clefts in the Bedouin population, with Spearman's correlation coefficient rank -0.9 (P < 0.01).

Conclusions: A significant decrease occurred in the incidence of facial clefts among Bedouin. This change may be attributed to prenatal care in the Bedouin Negev population as part of social and health-related behavior changes. The reduction in rates of congenital malformations, however, does not mean a reduction in the number of cases in a growing population. Also, with a modern western lifestyle, the expectancy and demand for reconstructive facial surgery and comprehensive care for these children are on the rise.