The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice.

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.

CAR-T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives.

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.

Outflow Reconstruction in Right Lobe Living Donor Liver Transplant: Middle Hepatic Vein Reconstruction Versus Separate Tributaries to Inferior Vena Cava Anastomosis.

OBJECTIVES: In right lobe living donor liver transplant, proper reconstruction of the segment 5 vein and segment 8 vein is essential. Herein, we compared 2 different techniques for segment 5 vein reconstruction. MATERIALS AND METHODS: This prospective nonrandomized study included all recipients of modified right lobe living donor liver transplant who had reconstruction of the segment 5 vein, with or without segment 8 veins, from October 2018 to October 2021. Patients were grouped into group A (classical technique) and group B (modified technique). For group A, the segment 5 (and segment 8, if present) vein was anastomosed in an end-to-side fashion to a polytetrafluoroethylene synthetic graft positioned parallel to the cut surface of the liver graft; then, during implant, its proximal end was anastomosed to recipient's middle hepatic or middle-left hepatic veins unified orifice. In group B (modified technique), the stumps of segment 5 (and segment 8 if present) were anastomosed in an end-to-end fashion to 2 different polytetrafluoroethylene grafts; then during implant, the other ends of the segment 5 grafts were anastomosed directly to the inferior vena cava. Postoperative segment 5 vein patency and graft recovery were compared. RESULTS: Forty patients were included: 22 in group A and 18 group B. There were no significant differences in the demographic data or characteristics of donors, grafts, and recipients between the groups. There was better patency in segment 5 synthetic grafts in group A at all time points compared with group B, but this difference was statistically significant only at 1 month (18 [81.8%] vs 9 [50%, respectively; P = .046).There was no statistically significant difference in the markers of graft recovery in both groups. CONCLUSIONS: Reconstruction of the segment 5 vein by polytetrafluoroethylene synthetic graft in a fashion to resemble the native middle hepatic vein in modified right lobe living donor liver transplant has better patency than anastomosis of the segment 5 vein in an end-to-end fashion to the synthetic graft and then to the inferior vena cava. Both techniques did not affect graft recovery.

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.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

Metabolic Syndrome in Behçets Disease Patients: Keep an Eye on the Eye.

BACKGROUND: Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/ sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's Disease (BD) remains unclear. AIMS: The aim was to determine the frequency of MetS among BD patients and to study its relationship with disease characteristics. METHODS: The study included 1028 adult BD patients recruited from 18 specialized rheumatology centers. 51 healthy matched control were considered. Behçet Disease Current Activity Form (BDCAF) and the BD damage index (BDI) were estimated. Adult Treatment Panel-III criteria were used to define MetS. RESULTS: The mean age of patients was 36.8 ± 10.1 years, M:F 2.7:1 and disease duration 7.01 ± 5.2 years. Their mean BDCAF was 5.1 ± 4.6 and BDI 5.5 ± 2.8. MetS was present in 22.8% of patients and in 5.9% of control (3.9 fold higher-risk). Patients with MetS had a significantly increased age at onset (31.8 ± 9.2 vs. 29 ± 8.5 years) and higher frequency of genital ulcers (96.2% vs. 79.7%), skin involvement (73.1% vs. 50.4%), arthritis (48.3% vs. 29.1%) (p<0.0001) and CNS manifestations (18.8% vs. 13%) (p=0.042) compared to those without it. Eye involvement was significantly increased in those with MetS (82.1% vs. 74.2%) (p=0.003) with increased frequency of posterior uveitis (67.1% vs. 43.5%), retinal vessel occlusion (35.9% vs. 21.3%), retinal vasculitis (41.9% vs. 26.4%) (p<0.0001) and vitritis (37.2% vs. 24%) (p=0.001). BDCAF was significantly lower (3.9 ± 4.3 vs. 5.6 ± 4.6) and BDI higher (7.4 ± 2.7vs5 ± 2.6) (p<0.0001). CONCLUSION: BD patients with MetS are predisposed to mucocutaneous, musculoskeletal, neuropsychiatric and ocular manifestations with consequently increased damage. The involvement of the deeper structures of the eye should alarm rheumatologists to keep in mind that all patients should have an eye examination, especially those with MetS.

Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.

OBJECTIVES: This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries. METHODS: The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed. RESULTS: The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents (p = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents (p = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries. CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.

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.

The impact of ExHp-CD (outer membrane vesicles) released from Helicobacter pylori SS1 on macrophage RAW 264.7 cells and their immunogenic potential.

Bacterial-derived extracellular vesicles could play a major role in attenuating and treating diseases. They play a major anti-infection role by modulating immune responses against pathogens and preventing infection by inhibiting pathogen localization and proliferation. In this study, outer membrane vesicles (ExHp-CD) released by Helicobacter pylori SS1 (H. pylori) and total antigens isolated from H. pylori SS1 (AgHp) were evaluated for their immunogenic potential and their effect on macrophage RAW 264.7 cells. Results demonstrated that both ExHp-CD and AgHp induced T helper 2 (Th2) immune response, which was reported to be important in immune protection against H. pylori infections. Both ExHp-CD and AgHp produced high levels of IL-10 and IL-4, while no significant levels of IL-12 p70 or IFN-γ were detected. However, ExHp-CD showed a better effect on macrophage RAW 264.7 cells compared to AgHp. Macrophage RAW 264.7 cells stimulated with 5, and 10 µg/mL of ExHp-CD showed an increased ratio of CD206 (M2 phenotype marker) and a decreased ratio of CD86 (M1 phenotype marker). Moreover, results suggested that the immunogenic effect that ExHp-CD possesses was attributed to their cargo of Epimerase_2 domain-containing protein (Epi_2D), Probable malate:quinone oxidoreductase (Pro_mqo), and Probable cytosol aminopeptidase (Pro_ca). Results demonstrated that ExHp-CD possesses an immunological activity to induce Th2 immune response against H. pylori infection with results comparable to AgHp. However, ExHp-CD showed higher efficacy regarding safety, biocompatibility, lack of toxicity, and hemocompatibility. Thus, it could serve as an immunogenic candidate with more desired characteristics.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint.

OBJECTIVE: The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. PATIENTS AND METHOD: This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. RESULTS: The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17-79 years), disease duration 4 years (0-75 years) while the median age at disease onset was 25 years (4-75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). CONCLUSION: SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

Rheumatologists' practice during the Coronavirus disease 2019 (COVID-19) pandemic: a survey in Egypt.

The aim of this work is to trace how rheumatologists all over Egypt are approaching the COVID-19 pandemic and what changes it has brought about in the patients' care with special attention to its effect on vulnerable rheumatic disease (RD) patients. This survey further aims to help inform the rheumatology community about the changes in practice during the COVID-19 pandemic. The survey included 26 questions distributed to University staff members across Egypt members of the Egyptian College of Rheumatology (ECR). It takes 5-10 min to fill out. The practice setting of participating rheumatologists included University Teaching Hospitals that are the main rheumatology and clinical immunology service providers for adults and children RD patients. There was an overall agreement across the country in the responses to the survey that took a median time of 7 min to fill in. Potential changes in rheumatology outpatient practice by staff members evolved since the COVID-19 pandemic. None of the university rheumatology staff members has prescribed chloroquine or HCQ to prevent or treat COVID-19 in a non-hospitalized patient who was not previously on it. Twenty-three recommended decrease/avoid NSAIDs if the RD patient had confirmed COVID-19 or symptoms. There is an agreement to the key emerging frontline role of rheumatologists in treating COVID-19. During the pandemic, RD cases requiring admission were dealt with by several modified strategies. The overall agreement among the different university rheumatology departments during such critical situation has provoked the ECR to consider providing provisional guidelines for dealing with RD patients during this global catastrophe.

Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer.

Growing experience with engineered chimeric antigen receptor (CAR)-T cells has revealed some of the challenges associated with developing patient-specific therapy. The promising clinical results obtained with CAR-T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti-tumor efficacy in CAR-T therapy. A potentially effective approach to improve the efficacy of CAR-T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR-T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR-T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR-T cell therapy and offer precision treatments against cancer.

Nanocellulose hyperfine network achieves sustained release of berberine hydrochloride solubilized with ß-cyclodextrin for potential anti-infection oral administration.

Berberine hydrochloride (BBH) has been used to treat diarrhea and other gastrointestinal diseases, however its therapeutic efficacy is compromised because of poor aqueous solubility and dissolution. In this work, BBH was solubilized with ß-cyclodextrin (ß-CD) in aqueous solution through formation of the BBH/ß-CD inclusion complex (IC), which was confirmed by the combination of different techniques including FT-IR, XRD, DSC, 1H NMR and 1H NOESY. The aqueous solubility of BBH at 25 °C was increased by ca. 102% in the presence of 16 mM ß-CD. BBH/ß-CD IC-loaded bacterial cellulose (BC) hydrogels (denoted as BC/IC) were prepared by physical absorption method, resulting in higher drug loading capacity (DLC) than BC/BBH hydrogels. In vitro drug release showed that sustained drug release was achieved at different pH conditions simulating the gastrointestinal fluids by BC/IC hydrogels due to the hyperfine network of BC matrix. Furthermore, in vitro anti-bacterial test demonstrated the BC/IC hydrogels induced effective bacterial inhibition. Together with the good biocompatibility and edibility of the BC matrix, these BC/IC hydrogels appear to be promising candidates of oral administration medicine against gastrointestinal infections.

Biopolymer-Based Microcarriers for Three-Dimensional Cell Culture and Engineered Tissue Formation.

The concept of three-dimensional (3D) cell culture has been proposed to maintain cellular morphology and function as in vivo. Among different approaches for 3D cell culture, microcarrier technology provides a promising tool for cell adhesion, proliferation, and cellular interactions in 3D space mimicking the in vivo microenvironment. In particular, microcarriers based on biopolymers have been widely investigated because of their superior biocompatibility and biodegradability. Moreover, through bottom-up assembly, microcarriers have opened a bright door for fabricating engineered tissues, which is one of the cutting-edge topics in tissue engineering and regeneration medicine. This review takes an in-depth look into the recent advancements of microcarriers based on biopolymers-especially polysaccharides such as chitosan, chitin, cellulose, hyaluronic acid, alginate, and laminarin-for 3D cell culture and the fabrication of engineered tissues based on them. The current limitations and potential strategies were also discussed to shed some light on future directions.

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].

Ocular anti-inflammatory activity of prednisolone acetate loaded chitosan-deoxycholate self-assembled nanoparticles.

Background and purpose: Conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. The aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (PA), to increase dosing accuracy, bioavailability, and accordingly, efficiency of PA in treating inflammatory ocular diseases. Methods: A novel formulation of self-assembled nanoparticles was prepared by the complexation of chitosan (CS) and, the counter-ion, sodium deoxycholate (SD), loaded with the poorly-water-soluble PA. Particle size, zeta potential, encapsulation efficiency (EE) and drug loading content (LC) of prepared nanoparticles were assessed. Moreover, the nanoparticles were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Drug release and eye anti-inflammatory potential of the prepared novel formulation was investigated. Results: Mean particle size of the nanoparticles have dropped from 976 nm ±43 (PDI 1.285) to 480 nm ±28 (PDI 1.396) when the ratio of CS-SD was decreased. The incorporation of 0.1-0.3% of polyvinyl alcohol (PVA), in the preparation stages, resulted in smaller nanoparticles: 462 nm ±19 (PDI 0.942) and 321 nm ±22 (PDI 0.454) respectively. DSC and FTIR results demonstrated the interaction between CS and SD, however, no interactions were detected between PA and CS or SD. Drug release of PA as received, in simulated tears fluid (pH 7.4), showed a twofold increase (reaching an average of 98.6% in 24 hours) when incorporated into an optimized nanoparticle gel formulation (1:5 CS-SD). Conclusion: The anti-inflammatory effect of PA nanoparticles loaded gel on female guinea pig eyes was significantly superior to that of the micronized drug loaded gel (P < 0.05).

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.

Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics.

With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.

Vasoplegic Shock Treated with Methylene Blue Complicated by Severe Serotonin Syndrome.

INTRODUCTION: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. However, the patient subsequently developed severe Serotonin Syndrome (SS) as a result of an interaction between serotonergic drugs and MB. CASE REPORT: A 15-year-old male developed severe vasoplegic shock 1.5 hours after overdosing on several different medications including quetiapine slow release, quetiapine immediate release, desvenlafaxine slow release, venlafaxine, amlodipine, ramipril, fluoxetine, promethazine and lithium. His vasoplegic shock was resistant to high doses of noradrenaline and vasopressin. MB was administered 6.5 hours post ingestion and within 1 hour there was an improvement in his hemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe Serotonin Syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor (MAO-I), and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours. CONCLUSION: MB is a useful additional strategy for severe drug induced vasodilatory shock and may be potentially life-saving. Clinicians should be aware that it can interact with other drugs and cause life-threatening Serotonin Syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction.