Giant cells in temporal artery biopsies and the risk of large vessel involvement in patients with giant cell arteritis.

OBJECTIVES: Giant cell arteritis (GCA) is a systemic disease with variable vascular involvement. The objective was to investigate predictors of time-dependent large vessel involvement (LVI) in a population-based cohort of patients with GCA. METHODS: GCA patients with positive temporal artery biopsies (TAB) between 1997- 2010 were identified through a regional pathology register. A structured review of histopathology reports and relevant imaging studies was performed. Cases with LVI through July 2016 were identified. Patients were followed to first LVI, death, migration from the area or July 29, 2016. Event free survival by clinical and histopathologic features was estimated using the Kaplan-Meier method. Potential predictors of LVI were examined using Cox regression models. RESULTS: A total of 274 patients were included. The mean age at GCA diagnosis was 75.7 years. Fifty-one patients (19 %) had documented LVI during the follow-up, corresponding to an incidence rate of 2.4/100 person-years. The median time from GCA diagnosis to the diagnosis of LVI was 4.5 years (interquartile range 0.6-7.4). Thirty-four patients had aortic involvement (67% of those with LVI; 12% of all GCA cases). Survival free of LVI was longer in patients with giant cells in the TAB (75th percentile 14.0 vs 6.7 years; p=0.014). In age-adjusted analysis, the presence of giant cells in the TAB was associated with reduced risk of LVI (hazard ratio 0.48; 95 % confidence interval 0.27-0.86). CONCLUSIONS: The negative association with giant cells in the TAB suggests that patients with LVI constitute a subset of GCA with particular disease mechanisms.

Evaluation of revised classification criteria for giant cell arteritis and its clinical phenotypes.

BACKGROUND: GCA is a systemic vasculitis of the elderly, viewed by many as a disease with multiple and overlapping clinical phenotypes. Retrospective studies have shown differences in clinical presentation between these phenotypes. To reflect the heterogeneity of GCA and novel diagnostic methods, new classification criteria have been proposed. METHODS: This is a retrospective study of newly diagnosed patients with GCA at the outpatient rheumatology clinics at Skåne University Hospital (Malmö and Lund) between 2012 and 2018. All patients were evaluated using two sets of classification criteria, the ACR classification criteria from 1990 and a proposed revision of these criteria requiring objective findings (positive biopsy or imaging) for classification. Patients were further classified as one of four widely used clinical phenotypes. RESULTS: A total of 183 patients with a new diagnosis of GCA were identified. The diagnosis was confirmed by one or two experienced rheumatologists in 116 of these patients during a review of medical records. The ACR criteria were more sensitive than the revised criteria (93.1% vs 72.4%), but the revised criteria had higher specificity (94.0% vs 28.4%). The revised criteria tended to have higher sensitivity in the phenotype with constitutional symptoms compared with cranial GCA (P = 0.08). CONCLUSION: The specificity of the ACR classification criteria for GCA can be improved by using revised criteria requiring objective findings of vasculitis. In addition, the wider symptoms covered by the revised criteria may improve classification of patients with a phenotype characterized by constitutional symptoms.

Development of intracranial vasculitis in giant cell arteritis during tocilizumab treatment.

Giant cell arteritis (GCA), a systemic large-vessel vasculitis, is a disease that has been treated with glucocorticoids since 1950. Over the years, several disease-modifying anti-rheumatic drugs have been evaluated as steroid-sparing agents with disappointing results. Tocilizumab, an interleukin-6 inhibitor, has in recent years been approved for the treatment of GCA. It remains uncertain whether the drug suppresses disease activity and maintains remission or just alleviates the symptoms and masks the signs of smoldering disease. This case describes the clinical findings at diagnosis and the course of the disease with the subsequent development of intracranial vasculitis in a 70-year-old male treated with tocilizumab. The present case illustrates the need for further studies regarding tocilizumab in the treatment of GCA patients and the need for meticulous evaluation at follow-ups.

Biosynthesis of Copper Oxide-Silver Nanoparticles from Ephedra Intermedia Extract and Study of Anticancer Effects in HepG2 Cell Line: Apoptosis-Related Genes Analysis and Nitric Oxide Level Investigations.

Liver cancer treatment faces significant obstacles such as resistance, recurrence, metastasis, and toxicity to healthy cells. Biometallic nanoparticles (NPs) have emerged as a promising approach to address these challenges. In this study, copper oxide-silver (Ag-doped CuO) NPs were prepared using a reduction method with Ephedra intermedia extract. The physicochemical properties of the NPs were evaluated using various techniques such as Field emission scanning electron microscopy (FESEM), Transmission Electron Microscope (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). Additionally, this study has evaluated nitric oxide levels (NO), reactive oxygen species (ROS) production, Bax, Bcl2, P53, and Caspase3 genes expression, as well as cell viability within 24 hours in liver cancer cell line HepG2. FESEM and TEM imaging confirmed the nanostructural nature of the synthesized particles with sizes ranging from 31.27 to 88.98 nanometers. XRD analysis confirmed the crystal structure of the NPs. Comparative analysis showed that the IC50 values of the Ag-doped CuO NPs were significantly lower than that of the plant extracts. Molecular studies showed significantly increased expression of Bax, Caspase3, and P53 genes, inducing apoptosis in cancer cells, and downregulation of Bcl2 as a pro-metastasis gene. Additionally, the presence of Ag-doped CuO NPs significantly increased NO activity enzyme and ROS generation compared to the plant extract. The biosynthesized Ag-doped CuO NPs demonstrated the ability to induce apoptosis, increase ROS production, and enhance NO enzyme activity in HepG2 cancer cells, suggesting their potential as a therapeutic agent for liver cancer.

Evaluating a targeted Palbociclib-Trastuzumab loaded smart niosome platform for treating HER2 positive breast cancer cells.

In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of -1.2 mV. Pal encapsulation reached ∼86%, and the release pattern followed a two-phase pH-dependent mechanism. MTT assessments demonstrated enhanced apoptosis induction, particularly in HER2-positive cells, by Trz-Pal-pHSNs. Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.

Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up.

BACKGROUND: The cause of diabetic foot ulcers is multifactorial, e.g., neuropathy and angiopathy, leading to functional disturbances in the macrocirculation and skin microcirculation. Adequate tissue oxygen tension is an essential factor in infection control and wound healing. Hyperbaric oxygen (HBO) therapy, daily sessions of oxygen breathing at 2.5-bar increased pressure in a hyperbaric chamber, has beneficial actions on wound healing including antimicrobial action, prevention of edema and stimulation of fibroblasts. The aim of the present study was to investigate the long-term effect of HBO in treatment of diabetic foot ulcers. METHODS: Thirty-eight diabetic patients (30 males) with chronic foot ulcers were investigated in a prospective study. The mean age was 60+/-13 years and the mean diabetes duration 27+/-14 years. All patients were evaluated with measurements of transcutaneous oxygen tension (tcPO(2)), peripheral blood pressure, and HbA(1c). All patients had a basal tcPO(2) value lower than 40 mmHg, which increased to >/=100 mmHg, or at least three times the basic value, during inhalation of pure oxygen. Seventeen patients underwent 40-60 sessions of HBO therapy, while 21 patients were treated conventionally. The follow-up time was 3 years. RESULTS: 76% of the patients treated with HBO (Group A) had healed with intact skin at a follow-up time of 3 years. The corresponding value for patients treated conventionally (Group B) was 48%. Seven patients (33%) in Group B compared to two patients (12%) in Group A went to amputation. Peripheral blood pressure, HbA(1c), diabetes duration, and basal values of tcPO(2) were similar in both groups. CONCLUSIONS: Adjunctive HBO therapy can be valuable for treating selected cases of hypoxic diabetic foot ulcers. It seems to accelerate the rate of healing, reduce the need for amputation, and increase the number of wounds that are completely healed on long-term follow-up. Additional studies are needed to further define the role of HBO, as part of a multidisciplinary program, to preserve a functional extremity, and reduce the short- and long-term costs of amputation and disability.