Immune Aging in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a life-long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self-tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto-destructive immunity in affected patients, including the process of immune aging.

Metabolic checkpoints in rheumatoid arthritis.

Background: Rheumatoid Arthritis is a systemic autoimmune disease affecting 0.5-1 % of the population. Despite a growing therapeutic armamentarium, RA remains incurable, and many patients suffer significant morbidity over time.

The Fourth Annual Symposium of the Midwest Aging Consortium.

The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023.

Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults.

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination.

Best timing of bilateral total hip arthroplasty - an analysis of revision and mortality rates from the German Arthroplasty Registry (EPRD).

Background: The burden of osteoarthritis (OA) in multiple joints is high and for patients with bilateral OA of the hip there is no clear recommendation about the indication for simultaneous (one-stage) bilateral total hip arthroplasty (THA) versus two-staged procedures. The purpose of this study was therefore to compare revision and mortality rates after different strategies of surgical timing in bilateral hip OA from the German Arthroplasty Registry (EPRD).

Methods: Since 2012 22,500 patients with bilateral THA (including 767 patients with one-staged bilateral surgery and 11,796 patients with another separate procedures within one year after first THA) are documented in the registry.

Save the subchondral bone plate: Debridement versus bone marrow stimulation in acetabular cartilage defects over 60 months of follow-up.

Purpose: Bone marrow stimulation is a common treatment for full-thickness cartilage defects in the hip joint. However, common procedures may result in poor fibrous repair tissue and changes to the subchondral anatomy. This study investigated the clinical outcome of a cohort of International Cartilage Repair Society (ICRS) grades 3 and 4 cartilage defects treated with bone marrow stimulation compared to those who received simple debridement/chondroplasty.

Feasibility and diagnostic accuracy of fast whole-body MRI in slightly to moderately injured trauma patients.

Objectives: To determine the feasibility and diagnostic accuracy of fast whole-body magnetic resonance imaging (WB-MRI) compared to whole-body computed tomography (WB-CT) in detecting injuries of slightly to moderately injured trauma patients.

Materials And Methods: In a prospective single-center approach, trauma patients from convenience sampling with an expected Abbreviated Injury Scale (AIS) score ≤ 3 at admission, received an indicated contrast-enhanced WB-CT (reference standard) and a plain WB-MRI (index test) voluntarily up to five days after trauma. Two radiologists, blinded to the WB-CT findings, evaluated the absence or presence of injuries with WB-MRI in four body regions: head, torso, axial skeleton, and upper extremity.

Immune checkpoints in autoimmune vasculitis.

Giant cell arteritis (GCA) is a prototypic autoimmune disease with a highly selective tissue tropism for medium and large arteries. Extravascular GCA manifests with intense systemic inflammation and polymyalgia rheumatica; vascular GCA results in vessel wall damage and stenosis, causing tissue ischemia. Typical granulomatous infiltrates in affected arteries are composed of CD4 T cells and hyperactivated macrophages, signifying the involvement of the innate and adaptive immune system.

PREX1 improves homeostatic proliferation to maintain a naive CD4+ T cell compartment in older age.

The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4+ T cell compartment into older age. Here, we describe that naive CD4+ T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age.

Patients risk for mortality at 90 days after proximal femur fracture - a retrospective study in a tertiary care hospital.

Background: Despite improving the management of proximal femur fractures (PFF) with legal requirements of timing the surgery within 24 h, mortality rates in these patients remain still high. The objective of our study was to analyze potential cofactors which might influence the mortality rate within 90 days after surgery in PFF to avoid adverse events, loss of quality of life and high rates of mortality.

Methods: In this retrospective, single-center study all patients with PFF aged 65 years and older were included.

Girdlestone resection arthroplasty for femoral neck fractures has poorer outcomes than hemiarthroplasty in frail patients with increased risk for arthroplasty-related complications: a retrospective case study of 21 patients.

Background And Purpose: Hemiarthroplasty (HA) is the usual treatment for displaced femoral neck fractures (FNF) in elderly patients. Patients may be unsuitable for HA due to secondary conditions such as systemic infections or severe neurological conditions, which is why Girdlestone resection arthroplasty (GRA) may be an option. We aimed to determine (1) patient survival in matched patient groups treated with either GRA or HA and (2) functional outcomes.

Stem-like CD4 T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis.

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown.

Heterogeneity of memory T cells in aging.

Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population.

Immune aging - A mechanism in autoimmune disease.

Evidence is emerging that the process of immune aging is a mechanism leading to autoimmunity. Over lifetime, the immune system adapts to profound changes in hematopoiesis and lymphogenesis, and progressively restructures in face of an ever-expanding exposome. Older adults fail to generate adequate immune responses against microbial infections and tumors, but accumulate aged T cells, B cells and myeloid cells.

T cell fate decisions during memory cell generation with aging.

The defense against infectious diseases, either through natural immunity or after vaccinations, relies on the generation and maintenance of protective T cell memory. Naïve T cells are at the center of memory T cell generation during primary responses. Upon activation, they undergo a complex, highly regulated differentiation process towards different functional states.

Senescent cells as thermostats of antitumor immunity.

Harnessing the immunogenic potential of senescent cells may be a viable but context-dependent opportunity to boost antitumor immunity.

Treatment of Severe Acetabular Defects With an Antiprotrusio Cage and Trabecular Metal Augments - Clinical and Radiographic Results After a Mean Follow-Up of 6.6 Years.

Background: Large acetabular bone defects present a serious challenge in revision total hip arthroplasty. The off-label use of antiprotrusio cages in combination with tantalum augments is a promising treatment option in these difficult situations.

Methods: Between 2008 and 2013, 100 consecutive patients underwent acetabular cup revision with a cage-augment combination in Paprosky 2 and 3 defect types (including pelvic discontinuities).

When are patients with osteoarthritis referred for surgery?

Current treatment strategies in hip and knee osteoarthritis (OA) involve a combined approach that includes not only modification of risk factors and conservative treatment but also joint-preserving surgical therapy in the early stages, or joint replacement in late OA. With the recent development of new etiological concepts (i.e.

CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging.

Chronic systemic inflammation is one of the hallmarks of the aging immune system. Here we show that activated T cells from older adults contribute to inflammaging by releasing mitochondrial DNA (mtDNA) into their environment due to an increased expression of the cytokine-inducible SH2-containing protein (CISH). CISH targets ATP6V1A, an essential component of the proton pump V-ATPase, for proteasomal degradation, thereby impairing lysosomal function.

Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis.

Loss of function of inhibitory immune checkpoints, unleashing pathogenic immune responses, is a potential risk factor for autoimmune disease. Here, we report that patients with the autoimmune vasculitis giant cell arteritis (GCA) have a defective CD155-CD96 immune checkpoint. Macrophages from patients with GCA retain the checkpoint ligand CD155 in the endoplasmic reticulum (ER) and fail to bring it to the cell surface.

[Hip dysplasia: What influence do age, arthrosis and concomitant diseases have on the treatment result?].

Pelvic osteotomies are an established treatment for symptomatic adult hip dysplasia with a promising long-term outcome. Results depend not only on the achieved acetabular reorientation but also on patient-factors like preoperative joint condition (degree of osteoarthritis and joint congruency) and age. Additionally, the diagnosis and appropriate therapy of impingement-associated hip deformities is essential in order to achieve good mid- and long-term outcomes.