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. hip dysplasia and femoroacetabular impingement as major risk factors for hip OA), treatment alternatives for joint preservation could be extended significantly. Satisfactory results of osteotomies and other reconstructive procedures around hip and knee joints can only be expected in early OA (Kellgren/Lawrence grade 0-II). If patients with advanced radiographic OA grades III-IV do not respond to conservative treatment over at least 3 months and express a relevant burden of disease, joint replacement might be considered. Prior to surgery, potential contraindications must be excluded, patient expectations need to be discussed, and modifiable risk factors, which may negatively influence the outcome, should be optimized.

[Complication profile and revision concepts for megaprosthetic reconstruction following tumour resection at the hip]. / Komplikationsprofil und Revisionsstrategien nach Tumorspezialendoprothetik am Hüftgelenk.

BACKGROUND: Tumourous destruction of the periacetabular region and the proximal femur is a typical consequence of either primary malignant bone tumour manifestation or skeletal metastatic diseases. Pathological fractures of the proximal femur and periacetabular regions due to primary manifestation or metastatic disorders are frequent. OBJECTIVES: Presentation of the most common complications of tumour endoprostheses at the hip and a description of management strategies, including therapeutic recommendations and concepts for complication avoidance. MATERIALS AND METHODS: The current knowledge and our own experience of complication management with the use of megaprostheses around the hip are presented. RESULTS: Compared to elective/primary total hip arthroplasty, megaprosthetic reconstructions following tumour resections have an increased rate of postoperative deep infections, dislocations, incidence of pathological and periprosthetic fractures and of deep vein thrombosis. The postoperative mortality and local tumour recurrence along with deep infections represent the most serious complications. CONCLUSIONS: In comparison to primary arthroplasty, the risk of failure and complications following tumour-endoprosthetic replacement is increased. Precise surgical planning and careful selection and preoperative preparation of suitable patients should be performed in close interdisciplinary cooperation with final decision-making on an interdisciplinary tumour board. Wide resection and advanced reconstruction, as well as complicated palliative stabilization due to malignant bone tumour growth around the hip joint should be performed in musculoskeletal tumour centres with profound expertise in osteosynthetic and endoprosthetic reconstruction and consecutive complication management of the pelvis and the proximal femur.

Biomechanical comparison of bi- and tricortical k-wire fixation in tension band wiring osteosynthesis.

BACKGROUND: Patients with a simple transversal fracture of the olecranon are often treated with a tension band wiring (TBW), because it is known as a biomechanically appropriate and cost-effective procedure. Nevertheless, the technique is in detail more challenging than thought, resulting in a considerable high rate of implant-related complications like k-wire loosening and soft tissue irritation. In the literature, a distinction is generally only made between transcortical (bi-) and intramedullary (mono-) fixation of the wires. There is the additional possibility to fix the proximal bent end of k-wire in the cortex of the bone and thus create a tricortical fixation. The present study investigates the effectiveness of bi- and tricortical k-wire fixation in a biomechanical approach. METHODS: TBW of the olecranon was performed at 10 cadaver ulnas from six donors in a usual manner and divided into two groups: In group 1, the k-wire was inserted by bicortical fixation (BC), and in group 2, a tricortical fixation (TC) was chosen. Failure behavior and maximum pullout strength were assessed and evaluated by using a Zwick machine. The statistical evaluation was descriptive and with a paired t test for the evaluation of significances between the two techniques. RESULTS: The average age of the used donors was 81.5 ± 11.5 (62-92) years. Three donors were female, and three were male. Ten k-wires were examined in BC group and 10 in the TC group. The mean bone density of the used proximal ulnas was on average 579 ± 186 (336-899) HU. The maximum pullout strength was 263 ± 106 (125-429) N in the BC group and increased significantly in the TC group to 325 ± 102 (144-466) N [p = .005]. CONCLUSION: This study confirms for the first time biomechanical superiority of tricortical k-wire fixation in the olecranon when using a TBW and may justify the clinical use of this method.

[Management of complications following tumor endoprosthetic replacement]. / Komplikationsmanagement nach Tumorendoprothesen.

BACKGROUND: Tumor endoprostheses are available as modular systems with which bone defects can be partially reconstructed, usually close to the joints, or as a total replacement of long tubular bones. As a result of continuously improved survival times, they are used with bone tumors, skeletal metastases and, increasingly, in revision arthroplasty. OBJECTIVES: Presentation of the most common complications of tumor endoprostheses and a description of their management, including treatment recommendations. MATERIALS AND METHODS: The current knowledge and our own experience of complication management with the use of megaprostheses are presented. RESULTS: The number of tumor endoprostheses procedures is limited, so that a limited number of studies and classifications are available. Periprosthetic infections involving the soft tissues represent the most serious failure after perioperative dying and local recurrence of the tumor. Two-stage revision remains the gold standard in periprosthetic infection, even if one-stage revision is justifiable in selective indications. Periprosthetic infection and local recurrence is associated with the risk of secondary amputations. Mechanical failure can be treated more easily. Specific socket systems for proximal femoral replacement and attachment tubing allow for adequate soft tissue reconstruction, restoration of joint function, and minimize the risk of dislocation. CONCLUSIONS: In comparison to primary arthroplasty, the risk of failure following tumor endoprosthetic replacement is increased but is basically controllable by revision surgery.

[Effects of serial mud baths on inflammatory rheumatic and degenerative diseases]. / Wirkeffekte serieller Heiltorfbäder bei entzündlich-rheumatischen und degenerativen Erkrankungen.

BACKGROUND: Mud baths have been used for a long time for the treatment of musculoskeletal diseases. In addition to a reduction of pain and improved function, serially applied mud baths lead to a reduction in the inflammatory processes, which often underlie degenerative and inflammatory rheumatic diseases. OBJECTIVE: This study investigated the effects of serial mud baths on parameters of functional health, on pain perception and at the molecular level in patients with inflammatory rheumatic diseases, e.g. rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and degenerative alterations, e.g. gonarthritis and/or coxarthritis. MATERIAL AND METHODS: A total of 41 patients with inflammatory rheumatic (33 RA and 8 AS) and 40 patients with degenerative diseases were subdived into 2 groups by computer-assisted randomization. In each group a subgroup received 9 serial mud baths within 21 days in addition to a multimodal physical rehabilitative complex treatment (intervention groups). In the other subgroups only the physical rehabilitative treatment was carried out and no mud baths were administered (control group). The outcome parameters were assessment of the functional capacity and pain perception (HAQ, FFbH, VAS and WOMAC), diesease activity (DAS28 and BASDAI) as well as laboratory markers of inflammatory activity (CRP, BSG, IL-1 beta and IL-10) and the patient assessment. RESULTS: In the intervention groups after serial mud baths there was a significant improvement in the functional parameters (HAQ and FFbH, both p < 0.01) and a significant reduction in pain strength (VAS, p < 0.01) persisting for 3 months after the end of treatment. A significant reduction in disease activity (RA in DAS28 and AS in BASDAI) could be shown for the intervention groups as well as the control groups, whereby the effect strength was more pronounced in the intervention groups. In patients with gonarthritis and/or coxarthritis a significant improvement in functional limitations (WOMAC, p < 0.01) was only found in the intervention groups. A significant improvement in the proinflammatory cytokine IL-1 beta (p < 0.01) was only found in the intervention groups with a simultaneous increase in the anti-inflammatory cytokine IL-10 (p < 0.01). The CRP and BSG remained within the normal range and showed no significant changes even after serial mud baths. CONCLUSION: Mud baths applied within the framework of a physical rehabilitative complex treatment brought about an improvement of parameters of functional health for both inflammatory rheumatic and degenerative diseases. Effects at the molecular level were induced, which are possibly accompanied by osteoprotective and chondroprotective effects.

Prospective randomized controlled trial in the treatment of lateral epicondylitis with a new dynamic wrist orthosis.

BACKGROUND: In the treatment of lateral epicondylitis (LE), the role of a new dynamic wrist orthosis is unclear. PATIENTS AND METHODS: Patients suffering from a LE longer than 3 months were multicentrically and prospectively randomized into a physiotherapeutic group (PT group) and in a physiotherapy group plus wrist orthosis (PT + O group). Physiotherapy consisted of daily eccentric strengthening exercises under initial professional supervision. Inclusion criteria were a Placzek score greater than 4. Exclusion criteria were previous surgery, rheumatic arthritis, elbow instability, radicular symptoms, higher-grade extensor tendon rupture, or cervical osteoarthritis. The clinical evaluation was performed after 12 weeks and 12 months. The Patient-Rated Tennis Elbow Evaluation (PRTEE) scale, Placzek Score, the pain rating (VAS), range of motion and the Subjective Elbow Score were evaluated. RESULTS: Of the initially 61 patients, 31 were followed up after 12 weeks and 22 after 12 months. Twenty-nine patients (43%) were male, the mean age was 46, and 44 patients (66%) had the right elbow involved. At 12 weeks, there was a pain reduction on the VAS in both groups (PT + O: 6.5-3.7 [p = .001]; PT: 4.7-4.1 [p = .468]), albeit it was only significant for the PT + O group. At 12 months, reduction was significant in both groups (PT + O: 1.1 [p = .000]; PT: 1.3 [p = .000]). The painless maximum hand strength in kg improved in both groups significant after 3 and 12 months. The Placzek score was reduced from 8.25 to 3.5 [p = .001] after 12 weeks for the PT + O group and from 8.1 to 3.8 [p = .000] in the PT group, as well as after 12 months in the PT + O group to 0 [p = .000] and in the PT group to 2.0 [p = .000]. The PRTEE improved in both groups after 12 weeks (PT + O: 52.8--31.3 [p = .002]; PT: 48.6-37.6 [p = .185]) and 12 months (PT + O: 16.15 [p = .000]; PT: 16.6 [p = .000]), although the reduction at 12 weeks was not significant for the PT group. CONCLUSION: The elbow orthosis appears to accelerate the healing process with respect to the PRTEE and pain on the VAS (12 weeks follow-up), although there is an adjustment after 12 months in both groups and a significant improvement of symptoms is achieved in all endpoints.

[Periacetabular osteotomy-what influence does age have on patient-relevant results? : A prospective 5­year investigation]. / Periazetabuläre Osteotomie ­ Welchen Einfluss hat das Alter auf patientenrelevante Ergebnisse? : Eine prospektive 5­Jahres-Untersuchung.

INTRODUCTION: Periacetabular osteotomy (PAO) is an effective procedure in treatment of symptomatic hip dysplasia. To achieve a good outcome a strict patient selection has to be applied. The aim of this study was to evaluate the influence of patient age at surgery on clinical outcome. METHODS: In a prospective study 86 patients (106 hips) underwent clinical and radiographic follow-up at a mean time of 5 years (2.5-8.5 years) after PAO. Patient-related outcome measurements (PROMs: EQ-5D, WOMAC, OHS, GTO) were applied preoperatively as well as postoperatively and the deformity correction as well as development of osteoarthritis were evaluated. In order to analyze the influence of patient age at surgery on clinical outcome, we subdivided the patient cohort into four different age groups (<20 years, 20-29 years, 30-39 years, >40 years). RESULTS: Of the patients 90% were very satisfied or satisfied with the results 5 years after surgery, and in all age groups PROMs significantly increased. Even though preoperative as well as postoperative algofunction declined in cohorts with increasing age, the overall benefit as measured in WOMAC and EQ-5D scores was equal in all age groups. Increasing age is associated with a progression in osteoarthritis as well as a higher conversion rate to total arthroplasty. DISCUSSION: Age is an important influencing factor on the long-term outcome after PAO. A certain age as cut off for indications could not be identified in this study. Even patients in the age groups 30-39 years and > 40 years showed PROM improvement and satisfaction with outcome at medium-term follow-up. The expected success rate has to be discussed preoperatively with the patient; however, as a higher conversion rate to hip arthroplasty as well as progressive osteoarthritis is associated with higher age, not only patient age alone but also morphological characteristics of the hip joint have to be taken into consideration.

The life cycle of a T cell after vaccination - where does immune ageing strike?

Vaccination is the optimal intervention to prevent the increased morbidity and mortality from infection in older individuals and to maintain immune health during ageing. To optimize benefits from vaccination, strategies have to be developed that overcome the defects in an adaptive immune response that occur with immune ageing. Most current approaches are concentrated on activating the innate immune system by adjuvants to improve the induction of a T cell response. This review will focus upon T cell-intrinsic mechanisms that control how a T cell is activated, expands rapidly to differentiate into short-lived effector cells and into memory precursor cells, with short-lived effector T cells then mainly undergoing apoptosis and memory precursor cells surviving as long-lived memory T cells. Insights into each step of this longitudinal course of a T cell response that takes place over a period of several weeks is beginning to allow identifying interventions that can improve this process of T cell memory generation and specifically target defects that occur with ageing.

[Arthroplasty for osteoarthritis secondary to hip dysplasia: Problem-oriented treatment strategies]. / Endoprothese bei Dysplasiecoxarthrose: Problemorientierte Versorgungsstrategien.

BACKGROUND: Because of anatomical variations total hip arthroplasty (THA) can be demanding in patients with osteoarthritis secondary to hip dysplasia. OBJECTIVES: Depending on the degree of bony deformation, hip dislocation and soft tissue alteration numerous treatment strategies are available. This review describes current approaches that address frequent deformities. MATERIALS AND METHODS: Review of relevant clinical studies, meta-analyses, and presentation of our own approach. RESULTS: Pre-operative planning (based on a thorough clinical and radiographic examination) is essential. Acetabular reconstruction close to the primary acetabulum should always be intended. Roof augmentation and/or cup medialization can support stable bony implant fixation. Subtrochanteric shortening osteotomy of the femur is a demanding but reliable technique that avoids nerve damage in cases where inappropriate lengthening would be necessary (i.e., high riding dislocation). CONCLUSIONS: Although the post-operative complication rate is elevated after THA for dysplastic hips compared with primary osteoarthritis, the overall functional results and implant survival are comparable.

[Total hip arthroplasty in overweight osteoarthritis patients]. / Die endoprothetische Versorgung beim übergewichtigen Koxarthrosepatienten.

BACKGROUND: An increasing number of patients scheduled for total hip arthroplasty (THA) are obese and exhibit a different risk profile from that of patients of normal weight. OBJECTIVES: To provide an overview of the impact of obesity on the outcome of primary THA. MATERIALS AND METHODS: Literature review and discussion of own epidemiological data. RESULTS: Obese patients can expect as much functional improvement as non-obese patients after THA. However, peri- and postoperative complication (e.g., periprosthetic infection and dislocation) rates are reported to be increased in obese THA patients. CONCLUSIONS: The knowledge of obesity-associated risks is the prerequiste for successful THA in obese patients.

[Update on metal-on-metal hip joints]. / Update Metall-Metall-Gleitpaarungen.

Increasing data are available describing risk factors for the development of local and systemic adverse events following operations using metal-on-metal (MoM) hip implants. The prevalence and clinical relevance of metal-associated problems are, however, still under debate. They can be influenced by type and position of implant as well as patient-specific factors. Patients with small MoM heads (maximum diameter 32 mm) and subgroups of resurfacing arthroplasty can achieve good long-term survival. The use of large head MoM implants (diameters greater than 36 mm), however, is currently not advised due to the unsatisfactory results.

[Avoidance, diagnostics and therapy of nerve lesions after total hip arthroplasty]. / Vermeidung, Diagnostik und Therapie von Nervenläsionen nach Hüftendoprothesenimplantation.

Nerve palsy following total hip arthroplasty is a rare complication. Developmental dysplasia of the hip, previous fracture treatment and medical comorbidities are characteristic risk factors. By accurate preparation of the patient and a careful operative technique nerve palsy can be avoided in most cases. Nerve palsy following poor patient positioning during the perioperative period should be avoided by close cooperation with anesthesiologists.In cases of postoperative nerve palsy correct diagnostics should be carried out immediately. Further treatment options should be considered to minimize the damage. For patients with definite nerve palsy, devices such as a foot drop splint are often necessary and should be carried out as soon as possible.

[Durom™ hip resurfacing. Short- to midterm clinical and radiological outcome]. / Durom™-Hüftoberflächenersatz. Kurz- bis mittelfristiges radiologisches und klinisches Ergebnisse.

BACKGROUND: Modern hip resurfacing as an alternative for stemmed total hip replacement therapy is associated with a specific risk profile. The aim of this study was therefore to assess the short- to midterm clinical and radiological outcome after introduction of the Durom™ Hip Resurfacing prosthesis in a consecutive series. MATERIALS AND METHODS: A total of 132 hips (119 patients, 34 female, mean age 48±8,3 years) were evaluated functionally (Harris Hip Score, UCLA and Tegner activity scores) and radiologically with a mean follow-up period of 29 (6-60) months. Furthermore, preoperative ASA- and Charnley-scores, perioperative parameters as well as complications were registered. RESULTS: During the observation period the Harris Hip Score improved by a mean of 36.6 points to 92.5±11.6 points (p<0.01). ULCA and Tegner scores improved by a mean of 3.1 and 1.6 to 7.1 and 4.0 points, respectively. Three patients (2.3%) needed revision surgery due to periprosthetic fracture, prosthesis infection, and aseptic loosening of the femoral component. In four patients (3.1%) an initial migration of the acetabular component not requiring surgical revision was observed radiologically. CONCLUSION: The Durom™ Hip Resurfacing prosthesis demonstrated a low revision rate and a good mid-term functional and radiological outcome. Due to acetabular cup migrations in a small number of patients we now use an implant with modified surface design.

Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome.

Response to immunosuppressive therapy (IST) in younger patients with myelodysplastic syndrome (MDS) has been linked to a T-cell-dominant autoimmune process that impairs hematopoiesis. Analysis of the age-adjusted CD4:CD8 ratio in 76 MDS patients compared with 54 healthy controls showed that inadequate CD4+, rather than expansion of CD8+ T cells, was associated with a lower ratio in a group that included both lower and higher risk MDS patients defined by the International Prognostic Scoring System. In younger MDS patients, naive and memory phenotypes defined by CD45RA and CD62L display showed depletion of naive CD4+ and CD8+ T cells, suggesting a possible relationship to IST responsiveness. To determine the correlation between T-cell subset distribution, T-cell turnover and autoimmunity, a cohort of 20 patients were studied before and after IST. The CD4:CD8 ratio correlated inversely with the proliferative T-cell index before treatment in IST-responsive patients, suggesting that proliferation may be linked to accelerated CD4+ T-cell turnover and hematopoietic failure. Our data show seminal findings that both CD4+ and CD8+ T-cell subsets are dysregulated in MDS. Association between these T-cell defects and response to IST suggests that aberrant T-cell homeostasis and chronic activation are critical determinants influencing autoimmune hematopoietic suppression in younger patients.

[Pathogenesis of medium- and large-vessel vasculitis]. / Pathogenese der Vaskulitis mittlerer und grosser Gefässe.

Giant cell arteritis (GCA), is a systemic vasculitis which preferentially targets large and medium branches of the upper-body aorta. Typical clinical manifestations result from arterial stenosis/occlusion causing blindness, stroke and aortic arch syndrome. Aortic involvement leads to dissection and aneurysm. On the cellular and molecular level, GCA is a sequel of abnormal innate and adaptive immune responses that occur in the specialized tissue niche of the arterial wall. Based on recent pathogenic studies, a novel disease model for GCA is emerging. It is now understood that the series of pathogenic events begins with dendritic cells (DC) indigenous to the artery's outer wall, leading to inflammatory vasculopathy. Placed close to the vasa vasorum, vascular DC are highly sensitive in recognizing pathogen-associated motifs assigning immune monitoring functions to blood vessels. Thus the large vessels are actively involved in immune monitoring. Each vascular territory expresses a unique profile of pathogen-sensing receptors, emphasizing functional diversity amongst structurally similar arteries. Innate immune stimulators can transform vascular DC into efficient antigen-presenting cells, attracting, activating, and instructing T lymphocytes to acquire tissue-invasive features. Macrophages provide critical tissue-damaging effector functions, directly injuring wall-residing cells and promoting a remodeling process that leads to intimal hyperplasia and luminal occlusion. Novel diagnostic and therapeutic approaches to GCA need to focus on the key position of vascular DC and the signals that break the immunoprivileged state of the vessel wall.

Immune-mediated mechanisms in atherosclerosis: prevention and treatment of clinical manifestations.

Accumulation of inflammatory cells identifies atherosclerotic plaque at risk for rupture. Typically, activated immune cells occupy the rupture-prone areas of the atherosclerotic lesion. These cells are an appealing therapeutic target for novel strategies of plaque stabilization. Biologic consequences of plaque inflammation ultimately depend not only on the cellular players populating the lesion but also on triggers of immune activation originating from within the plaque or arriving from the circulation, and immune effector mechanisms that mediate cellular damage and plaque destabilization. Recent studies have provided insights into particular immune mechanisms in the atherosclerotic plaque that contribute to plaque vulnerability. This knowledge provides the basis for potential immunomodulatory therapies in cardiovascular disease. These therapeutic approaches can be classified as (1) immunomodulatory effects of existing therapies, (2) therapies targeting inflammatory triggers, and (3) agents inhibiting specific immune mechanisms.

VEGF gene polymorphisms and susceptibility to rheumatoid arthritis.

OBJECTIVES: To investigate polymorphisms of the VEGF gene in patients with rheumatoid arthritis (RA), their relationship to clinical features and the radiographic progression of joint disease. METHODS: One hundred and forty patients with RA and 149 healthy unrelated controls were recruited. We examined four polymorphisms of the VEGF gene which are reported to be associated with production of vascular endothelial growth factor (VEGF), using polymerase chain reaction (PCR) restriction fragment length polymorphism assay and amplification refractory mutation system (ARMS) PCR. Haplotypes were predicted by Bayesian algorithm using the Phase program. RESULTS: All four polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of the 936 T allele, which has been associated with lower production of VEGF, was significantly increased in RA patients compared with controls (22.7 vs 13.4%, P = 0.002). The frequencies of two haplotypes (CGCT and AAGT) which were predicted using the Phase program were significantly increased in RA patients compared with controls [33 vs 14%, odds ratio (OR) 2.636, 95% confidence interval (CI) 1.38-5.04 for CGCT; 17 vs 6%, OR 3.08, 95% CI 1.20-7.92 for AAGT]. The carriers of the susceptible haplotypes in RA patients had a younger age at disease onset but did not show a difference in the progression rate of radiographic joint destruction. CONCLUSIONS: Our data suggest that the VEGF gene may play a role in the development of RA

How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial.

OBJECTIVE: To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis (RA). METHODS: Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr. None of the patients had previously received disease-modifying anti-rheumatic drugs (DMARDs). All patients were assigned to receive hydroxychloroquine (HCQ) at enrollment, and could also take non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. At any point during follow-up, patients not fulfilling the American College of Rheumatology (ACR) 50 criteria for improvement and/or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate (MTX), 7.5-20 mg/week. Clinical, laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated. RESULTS: After 24 months of follow-up, a majority of patients (56/94) were either still on solo DMARD therapy with HCQ (n = 49) or off DMARD therapy with controlled/quiescent disease (n = 4), and 38 patients were taking MTX (including 11 in combination with other DMARDs). At month 24, all but 9 patients met ACR50 criteria for treatment response. Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score, baseline rheumatoid factor titre > 1:40, higher number of swollen joints, and poor patient global assessment. The presence of HLA-C7xx at enrollment was also predictive of need for MTX therapy. CONCLUSIONS: This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA. There continue to be very few consistently reliable predictors of treatment needs in patients with this disease.

The power of the third dimension: tissue architecture and autoimmunity in rheumatoid arthritis.

Lymphoid organs are the anatomic solution to the challenge of responding to minute amounts of antigen with powerful effector mechanisms. By arranging interacting cells in complex three-dimensional topographies lymphoid organs provide an optimal match between form and function. This principle is exploited in ectopic lymphoid structures that characteristically appear in rheumatoid synovitis. Synovial tissue T cells and B cells cooperate in different types of lymphoid organizations. Dendritic cell networks in the inflamed synovial membrane optimize antigen collection, storage, processing, and presentation. Synovial tissue cells participate in lymphocyte recruitment and the formation of tissue architectures that amplify immune responses. Recent data support the concept that the tissue organization in the rheumatoid joint fosters a breakdown in self-tolerance by promoting a phase transition from self-limited immune responses to self-perpetuating autoimmune responses.

Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals.

Elderly individuals are at high risk for morbidity and mortality when infected with influenza virus. Vaccinations with inactivated virus are less effective in the elderly due to the declining competency of the aging immune system. We have explored whether immunological parameters predict poor anti-influenza virus vaccine responses and can be used as biological markers of immunosenescence. One hundred fifty-three residents of community-based retirement facilities aged 65 to 98 years received a trivalent influenza vaccine. Vaccine-induced antibody responses were determined by comparing hemagglutination inhibition titers before and 28 days after immunization. The composition of the T-cell compartment was analyzed by flow cytometry and the sizes of three T-cell subsets, CD4(+) CD45RO(+) cells, CD4(+) CD28(null) cells, and CD8(+) CD28(null) cells, were determined. Only 17% of the vaccine recipients were able to generate an increase in titers of antibody to all three vaccine components, and 46% of the immunized individuals failed to respond to any of the three hemagglutinins. The likelihood of successful vaccination declined with age and was independently correlated with the expansion of a particular T-cell subset, CD8(+) CD28(null) T cells. The sizes of the CD4(+) CD45RO(+) memory T-cell and CD4(+) CD28(null) T-cell subsets had no effect on the ability to mount anti-influenza virus antibody responses. Frequencies of CD8(+) CD28(null) T cells are useful biological markers of compromised immunocompetence, identifying individuals at risk for insufficient antibody responses.