Development of machine learning models for detection of vision threatening Behçet's disease (BD) using Egyptian College of Rheumatology (ECR)-BD cohort.

BACKGROUND: Eye lesions, occur in nearly half of patients with Behçet's Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. METHODS: Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. RESULTS: A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. CONCLUSIONS: Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.

Cardiac magnetic resonance imaging in patients with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystemic vasculitis that may affect the heart. However, the incidence and nature of cardiac involvement in BD have not been clearly documented yet. The aim of this study was to delineate the cardiac magnetic resonance imaging (MRI) appearances of cardiac involvement in BD patients. METHODS: This cross-sectional observational study was carried out 30 BD patients without known cardiac disease. Patients were subjected to history taking, physical examination, echocardiography and cardiac MRI. RESULTS: At least one abnormality on cardiac MRI was observed in 20/30 patients (66.67%). Myocardial oedema was observed in 3 patients (10%) and late gadolinium enhancement in 1 patient (3.3%). Pericardial effusion was found in 3 patients (10.0%), global hypokinesia in 6 patients (20.0%) and intra-cardiac thrombosis in only 1 patient (3.3%). Pulmonary artery was dilated in 4 patients (13.3%). Left ventricular (LV) and right ventricular (RV) end diastolic volume were altered in 4 patients (13.3%) and 7 patients (23.3%) respectively. LV and RV end systolic volume were abnormal in 7 patients (23.3%) and 5 patients (16.7%) respectively. There was aortic valve regurge in 2 patients (6.7%), tricuspid valve regurge in 9 patients (30%), and mitral valve regurge in 9 patients (30%). Dilated left main coronary artery was found in 2 patients (6.7%) and arrhythmogenic right ventricular dysplasia in only one patient 1 patient (3.3%). On logistic regression analysis, BD activity index score was a significant predictor of cardiac abnormalities. CONCLUSION: BD may cause cardiac abnormalities without clinical manifestations and cardiac MRI may represent a tool for early detection of these subtle abnormalities. Higher BD activity index scores are strongly linked to cardiac problems.

Development and validation of a Behçet's Disease Damage Index for adults with BD: An Explicit, Composite and Rated (ECR) tool.

BACKGROUND: Behçet's disease (BD) is a chronic multisystem variable vessel vasculitis. Disease damage is irreversible and permanent. Validated tools evaluating damage are limited. Enhancements in the clinical treatment of vasculitis will take place from the development of refined and exclusive indices for individual vasculitic syndromes including BD and attempting their international validation. OBJECTIVES: This aim was to develop and validate a simple BD Damage Index (BDI). METHODS: This was a nationwide study including 1252 BD patients. The work consisted of 3 stages. Stage 1: items generation for score content. Stage 2: items selection for the draft score was performed by an expert rheumatologist. Stage 3: the content validity of the draft score was assessed and BDI, Vasculitis Damage Index (VDI), Antineutrophil cytoplasmic antibody-associated Vasculitis Index of Damage (AVID) and Combined Damage Assessment Index (CDAI) were calculated and compared. RESULTS: The mean age of the BD patients was 36.1 ± 9.9 years. Stages 1 and 2 resulted in a BDI instrument containing 73 items with a maximum score of 100. Stage 3, the VDI, CDAI, AVID, and BDI were 2.9 ± 2.2, 3.1 ± 2.3, 3.1 ± 2.3 and 5.1 ± 2.9, respectively. High correlations (r = .9) between comparable damage scores assured acceptable concurrent validity. CONCLUSION: The proposed BDI represents a new robust and potentially useful tool when dealing with BD chronic status.

Combining Low Power Fractional CO2 With QS-NdYAG Toning in the Treatment of Melasma Reduces the Incidence of Punctate Leukoderma.

BACKGROUND AND OBJECTIVES: Q-switched Nd:YAG (QS-Nd:YAG) toning (low fluence, large spot size, and high frequency) has been used successfully for the treatment of melasma, especially in dark skin phototypes. Punctate leukoderma was found to be a frequent complication that reduced the safety of this procedure. Combining low power fractional CO2 laser, which is another effective melasma laser therapy, might improve the efficacy and safety of this procedure. The aim of this study was to evaluate  the effect of combining low power fractional CO2 laser with QS-Nd:YAG toning in the treatment of melasma. STUDY DESIGN/MATERIALS AND METHODS: A randomized comparative split-face study included a total of 30 patients with bilateral, symmetrical melasma. All patients received QS-Nd:YAG toning on one randomly selected side of the face, while the other side randomly received either low power fractional CO2 alone (group A) or combined QS-Nd:YAG toning with low power fractional CO2 (group B). QS-Nd:YAG toning sessions were scheduled every two weeks for nine consecutive sessions, and low power fractional CO2 sessions were received every 4 weeks for three consecutive sessions. The assessment was done using the modified melasma area and severity index (mMASI) score, spectrophotometry (melanin index [MI] and erythema index [EI]), photography, blinded physician assessment, and patient satisfaction (at baseline, 1 week and 8-12 weeks after the last treatment sessions). RESULTS: A significant reduction in the mMASI score and MI was obtained with all treatment regimens. On comparing different modalities, group A reduction in mMASI and MI was significantly greater on the side receiving QS-ND:YAG toning (64.03% and 8.27%, respectively), than the side receiving low power fractional CO2 laser alone (36.02%. 2.64%, respectively). On the other hand, reduction of mMASI score and MI showed no statistical significance between the side receiving QS-Nd:YAG toning alone and the combined modality. Punctate leukoderma occurred in four cases (13%) on the side receiving QS-Nd:YAG toning. CONCLUSION: QS-Nd:YAG toning is significantly more effective than low power fractional CO2 in the treatment of melasma when used separately. Although combining low power fractional CO2 with QS-Nd:YAG toning does not increase its efficacy, it minimizes the incidence of the undesirable punctate leukoderma complication and achieves lower recurrence. This combination can thus be recommended as a safe and effective measure for the treatment of melasma. © 2021 Wiley Periodicals LLC.

Correction to: Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.

The author wishes to correct the record and clarify that in the original version of this article in the Discussion section under "Prevalence over the country governorates" inadvertently presented incorrect data cited in the reference [30].

Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.

OBJECTIVES: The present work was conducted to estimate the prevalence of adult Behçet's disease (BD) in adult Egyptian and to study the clinical pattern and influence of age at-onset and sex on disease phenotype. Also, we investigated the spectrum of presentation and frequencies along the north-to-south gradient of the country. PATIENTS AND METHOD: The population-based, multicenter, cross-sectional study included 1526 adult BD patients from 26 specialized Egyptian rheumatology centers. Demographic, clinical, and therapeutic data are assessed for all patients. RESULTS: The mean age of patients was 35.7 ± 9.84 years, disease duration 6.58 ± 5.25 years, and age at onset 29.37 ± 8.6 years; 91 were juvenile-onset (JoBD). There were 1102 males and 424 females (M:F 2.6:1). Regarding co-morbidities, 19.92% were diabetic, and 26.05% were hypertensive. The mean body mass index was 27.57 ± 5.24 (43.1% overweight; 25.9% obese). The mean BD current activity form was 4.48 ± 4.28. Regarding the medications use, systemic steroid and colchicine were the most common drugs used (947 (90.2%) and 611 (82.7%), respectively). The overall estimated prevalence of BD in Egypt was 3.6/100,000 population being highest in the two main cities: Alexandria (15.27) and Cairo (8.72). Pathergy test was positive in 43.4%. 90.2% were receiving systemic steroids and 8.3%, biologics. Disease characteristics were comparable between JoBD and adult-onset BD cases. Central nervous system (CNS), deep venous thrombosis (DVT), and gastrointestinal (GIT) involvement were significantly higher in males (p = 0.01, p = 0.001, and p = 0.001 respectively) while joint affection (p = 0.001) and disease activity (p = 0.011) were increased in females. CONCLUSIONS: This study provides current prevalence of BD in Egypt; 3.6/100,000 with no remarkable north-to-south gradient. The sex influences the disease phenotype with the CNS, DVT, and GIT involvement are higher in males, while the joint affection and disease activity were increased in females. KEY POINTS: • The prevalence and phenotype of Behçet's disease across Egypt is presented in a multicenter nationwide study. • The potential influence of the age at onset and sex on disease phenotype is highlightened. • A review of the literature worldwide is presented allowing comparisons with studies from other nations.

Th17 and IL-17 as Predictors of Hepatic Inflammation in Patients with Chronic Hepatitis C Virus Infection and Treated With Direct Antiviral Therapy.

Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with regard to hepatic inflammation and fibrosis. We aimed to investigate the relationship between circulating and intrahepatic frequency of Th17 cells and IL-17 serum level and degrees of hepatic inflammation and fibrosis in chronic HCV patients, as well as to evaluate the effect of successful anti-viral therapy on these parameters. This nested longitudinal case control study included 30 treatment-naïve chronic HCV patients and 20 healthy individuals as control. All patients were investigated for circulating Th17 cell percentage (flow cytometry) and intrahepatic Th17 cell percentage (immunohistochemistry) and serum IL-17 (ELISA) at baseline and at week 12 after discontinuation of therapy. Circulating and intrahepatic Th17 cell percentage and serum IL17 level were found to be significantly higher in chronic HCV patients when compared with controls, with significant correlation with Metavir activity score. No patients required discontinuation of therapy due to any adverse event allowing for sustained virological response at 12 weeks (SVR12) in 24 patients while the remaining six patients were considered "non-responders". Circulating Th17 cells and serum IL17 levels were significantly decreased after successful Sofosbuvir-Ribavirin therapy (P < 0.0001). The extent of liver inflammation is positively correlated with frequencies of circulating Th17 cells, and their HCV-specific IL17 secretion, and intrahepatic Th17 cells. This data may also provide the basis for the potential use of Th17 as a new marker for disease advancement of chronic hepatitis C.

Serum soluble toll-like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus-related cardiovascular dysfunction.

AIM: To assess the serum levels of soluble toll-like receptor (sTLR2) as an endogenous negative regulator of TLR2 signaling in systemic lupus erythematosus (SLE) patients, to investigate the correlation between sTLR2 and SLE disease activity index (SELDAI), SLE-related cardiovascular risk factors and ventricular dysfunction and to evaluate the effect of different therapeutic regimens on serum sTLR2 levels. METHODS: Ninety-six SLE patients, along with 30 healthy controls, were enrolled in the study. Echocardiography measurements were performed. Serum levels of (sTLR2) were measured using enzyme-linked immunosorbent assay (ELISA). Serum lipid profiles, uric acid and creatinine were also detected. RESULTS: Mean serum levels of sTLR2 in SLE patients was 3.98 ± 4.4 ng/mL, which was significantly decreased as compared with that of the control group (11.3 ± 4.9 ng/mL; P < 0.0001). sTLR2 was negatively correlated with SELDAI, low-density lipoprotein (LDL) and left ventricular diastolic dysfunction. sTLR2 levels were increased in patients receiving hydroxychloroquine, statins and corticosteroids. CONCLUSION: Serum sTLR2 can attenuate disease activity and negatively impact left ventricular diastolic dysfunction and hypercholersterelemia in SLE patients. Statins, corticosteroids and chloroquine increase sTLR2 levels.

Effect of peroxisome proliferator-activated receptor gamma agonist (pioglitazone) and methotrexate on disease activity in rheumatoid arthritis (experimental and clinical study).

OBJECTIVE: To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. METHODS: EXPERIMENTALLY: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. RESULTS: Pioglitazone produced a significant improvement of serum oxidative stress parameters (P < 0.05), and inflammatory cytokines in the treated arthritic group (P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 (P = 0.001) and C-reactive protein (P < 0.0001) compared to placebo group. CONCLUSION: The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.

Insulin resistance in early untreated rheumatoid arthritis patients.

OBJECTIVES: To assess insulin resistance in early untreated rheumatoid arthritis patients and its relation to the clinical, inflammatory and biochemical characteristics of these patients. PATIENTS AND METHODS: Sixty-six untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year along with age and sex matched controls were studied. Disease activity score (DAS28) was used to assess disease activity. Plasma levels of C- reactive protein (CRP), glucose, insulin and complete lipid profile were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: RA patients revealed high grade systemic inflammation compared to control group p<0.0001. Patients with high disease activity were more insulin resistant than patients with moderate disease activity P<0.0001. CONCLUSION: The findings of the present study showed that early untreated RA patients are characterized by a severe insulin resistant state that is driven primarily by disease activity and systemic inflammation.

Prognostic significance of FLT3 internal tandem duplication in egyptian patients with acute myeloid leukemia with normal or favorable risk cytogenetics.

Internal tandem duplication (ITD) of the FLT3 gene (FLT3/ITD) has been linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate. The aim of this study was to evaluate the prognostic significance of FLT3/ITD in patients with de novo AML and normal or favorable risk cytogenetics (NFC-AML). Blood samples from 39 patients with AML were subjected to PCR of exons 14 and 15 of the FLT3 gene. Patients included 25 with normal cytogenetics, 8 with t(15;17), 4 with t(8;21) and 2 with inv(16). FLT3/1ITD was found in 6/39 (15.4%) patients, 4 of them showed normal cytogenetic, 1 positive for t(15;17) and 1 positive for t(8;21). Patients were M1 3/13, M2 2/12, M3 1/9, M4 0/4 and M5 0/1. The patients were followed up for a mean of 34.5 +/- 2.3 months. The complete remission (CR) rates for the FLT3/ITD+ and FLTITD- groups were 50% vs 63.6%, while the relapse rates were 50% vs 28.6% respectively. Interestingly, disease free survival (DFS) at 3 years was significantly different in studied patients: DFS was 5% in patients with FLT3/ITD+ vs 30% of patients with FLT3/ITD- (P = 0.001). Our data suggest a possible high prognostic value of FLT3/ITD in patients with normal/favorable cytogenetics.