Does tocilizumab eliminate inflammation in GCA? A cohort study on repeated temporal artery biopsies.

Background: Vascular inflammation persists in temporal artery biopsy (TAB) of giant cell arteritis (GCA) patients even after prolonged glucocorticoid (GC) therapy. We aimed to evaluate the histological impact of adding tocilizumab (TCZ) to GCs.

Methods: We enrolled all consecutive GCA patients with an inflammed TAB at diagnosis who were treated with TCZ and GCs for ≥6 months and followed from December 2017 to December 2023.

Effects of Maltodextrin-Fructose Supplementation on Inflammatory Biomarkers and Lipidomic Profile Following Endurance Running: A Randomized Placebo-Controlled Cross-Over Trial.

Background: Managing metabolism for optimal training, performance, and recovery in medium-to-high-level endurance runners involves enhancing energy systems through strategic nutrient intake. Optimal carbohydrate intake before, during, and after endurance running can enhance glycogen stores and maintain optimal blood glucose levels, influencing various physiological responses and adaptations, including transitory post-endurance inflammation. This randomized trial investigates the impact of a high-dose 2:1 maltodextrin-fructose supplementation to medium-to-high-level endurance runners immediately before, during, and after a 15 km run at 90% VO intensity on post-exercise inflammatory stress.

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis.

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: results from the extension of the TOPAZIO study.

Objectives: To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA).

Methods: 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period.

Ultrasound Examination of Common Carotid Adventitial Thickness Can Differentiate Takayasu Arteritis and Large Vessel Giant Cell Arteritis.

Pathological studies have demonstrated that the adventitial layer is markedly thickened in Takayasu (TAK) as compared to large vessel giant cell arteritis (LV-GCA). An ultrasound (US) examination of the arterial vessels allows the determination of intima media thickness (IMT) and of adventitial layer thickness (extra media thickness (EMT)). No previous study has evaluated if there are differences in EMT thickness between TAK and LV-GCA.

Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Precision Delivery of Human Bone Marrow-Derived Mesenchymal Stem Cells Into the Pancreas Via Intra-arterial Injection Prevents the Onset of Diabetes.

Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect.

Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP.

Eosinophilic giant cell arteritis: A different subset of disease?

Objectives: To describe the clinical findings, response to therapy and course of patients with transmural eosinophilic infiltration at temporal artery biopsy (TAB).

Methods: The study consisted of a retrospective cohort of 254 consecutive GCA patients with evidence of transmural inflammation at TAB seen at the Santa Maria Nuova Hospital over a 28-year period. The findings of the 22 patients with eosinophilic infiltration (≥ 20 eosinophils/hpf) at TAB were compared with those of 232 patients without.

Effectiveness and safety of a 26-week taper regimen of glucocorticoid in GCA patients: Results from a prospective cohort study.

Objectives: To assess the effectiveness and safety of the 26-week tapering regimen of glucocorticoids (GC) used in the GiACTA trial in a prospective cohort of treatment-naive, biopsy-proven GCA patients.

Methods: Patients with a new diagnosis of biopsy-proven GCA enrolled in the GC arm of the START project (molecular stratification of patients with GCA to tailor GC and tocilizumab therapy) were included. All patients were treated with the 26-week taper regimen of GC used in the GiACTA trial.

Development of the Takayasu Arteritis Integrated Disease Activity Index.

Objective: Accurate clinical assessment of disease activity in Takayasu arteritis (TAK) can be challenging. F-fluorodeoxyglucose-positron emission tomography (FDG-PET) can directly measure vascular inflammation. This study details the development of a new type of disease activity index called the Takayasu's Arteritis Integrated Disease Activity Index (TAIDAI).

Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

Objectives: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients.

Methods: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed.

Impact of GAD65 and IA2 autoantibodies on islet allograft survival.

Introduction: Islet transplantation (ITx) shows promise in treating T1D, but the role of islet autoantibodies on graft survival has not been clearly elucidated. We aimed to analyze the effect of GAD65 and IA2 autoantibody status on graft survival and attainment of insulin independence in subjects with T1D who underwent ITx.

Method: We conducted a retrospective cohort study on 47 ITx recipients from 2000 to 2018.

Dynamic scRNA-seq of live human pancreatic slices reveals functional endocrine cell neogenesis through an intermediate ducto-acinar stage.

Human pancreatic plasticity is implied from multiple single-cell RNA sequencing (scRNA-seq) studies. However, these have been invariably based on static datasets from which fate trajectories can only be inferred using pseudotemporal estimations. Furthermore, the analysis of isolated islets has resulted in a drastic underrepresentation of other cell types, hindering our ability to interrogate exocrine-endocrine interactions.

Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles (MSC-sEVs): A Promising Treatment Modality for Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is associated with neuropathy and/or peripheral artery disease of the lower limb in diabetic patients, affecting quality of life and leading to repeated hospitalizations and infections [...

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation.

Reversal of Experimental Autoimmune Diabetes With an sCD39/Anti-CD3 Treatment.

Extracellular (e)ATP, a potent proinflammatory molecule, is released by dying/damaged cells at the site of inflammation and is degraded by the membrane ectonucleotidases CD39 and CD73. In this study, we sought to unveil the role of eATP degradation in autoimmune diabetes. We then assessed the effect of soluble CD39 (sCD39) administration in prevention and reversal studies in NOD mice as well as in mechanistic studies.

Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders.

Omega-3 polyunsaturated fatty acids (PUFA) have demonstrated anti-inflammatory properties, while Omega-6 have pro-inflammatory effects, and the balance between the two is an important aspect of healthy nutrition. Over the last 30 years, however, the Western diet has shifted largely from Omega-3 to Omega-6 consumption. Uncontrolled aberrant and chronic inflammation is a leading component of many common diseases, including arthritis, cardiovascular diseases, neurodegenerative diseases, cancer, obesity, autoimmune diseases, and infective diseases.

HLA-B Matching Prolongs Allograft Survival in Islet Cell Transplantation.

Islet cell transplantation (ITx) is an effective therapeutic approach for selected patients with type 1 diabetes with hypoglycemia unawareness and severe hypoglycemia events. In organ transplantation, human leukocyte antigen (HLA) mismatching between donor and recipient negatively impacts transplant outcomes. We aimed to determine whether HLA matching has an impact on islet allograft survival.

Steroid-sparing agents in polymyalgia rheumatica: how will they fit into the treatment paradigm?

Introduction: Polymyalgia rheumatica is a common inflammatory rheumatic disease in subjects aged 50 years or older and classically presents with shoulder and/or pelvic girdle pain and prolonged morning stiffness. Glucocorticoids represent the standard of treatment; glucocorticoid therapy is usually required for 1-2 years and often results in significant glucocorticoid-related side effects, especially in the elderly.

Areas Covered: In this review, we aimed to provide a comprehensive overview of the management of polymyalgia rheumatica, with a particular focus on adjunctive therapies to the standard glucocorticoid treatment.

Prolonged clinical remission of type 1 diabetes sustained by calcifediol and low-dose basal insulin: a case report.

Herein, we describe an unusually prolonged duration (31 months) of the clinical remission phase in a 22-year-old Italian man with new-onset type 1 diabetes. Shortly after the disease diagnosis, the patient was treated with calcifediol (also known as 25-hydroxyvitamin D3 or calcidiol), coupled with low-dose basal insulin, to correct hypovitaminosis D and to exploit the anti-inflammatory and immunomodulatory properties of vitamin D. During the follow-up period, the patient retained a substantial residual β-cell function and remained within the clinical remission phase, as evidenced by an insulin dose-adjusted glycated hemoglobin value <9.

The potential therapeutic role of vitamin D in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is defined as a relapsing and remitting condition characterized by chronic inflammation at different sites in the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) represents the two major forms of IBD. Even though IBD pathophysiology is still not fully understood, genetic factors, environmental factors, dysregulation of both innate and adaptive immune responses, alterations in gut microbiota composition, excessive consumption of saturated fats and cumulative antibiotic exposure have all been suggested to play a role in the development of this condition.