Intraarticular Inflammation and Catabolic Markers in Femoroacetabular Impingement during Progression of Disease -comparison between early and late stage disease-

Objectives: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of osteoarthritis hips (OA). Inflammation is thought to be one of the main initiators of hip OA, yet little is known about the location and progression of intraarticular inflammation in FAI hips. The aim of this study is to characterize inflammation and catabolic markers in the early and late stage of FAI hips in patients with symptomatic Cam FAI. Methods: Head-neck cartilage, acetabular cartilage, and synovial samples were obtained from 30 patients undergoing hip surgery. Fifteen patients had a diagnosis of symptomatic Cam FAI (early FAI-symptomatic FAI) and 15 presented with advanced OA secondary to Cam FAI (late FAI/secondary OA). Control cartilage samples were procured from the head-neck junction of 7 osteochondral fresh allografts from healthy young-adult donors (control). Radiographically, the α-angle was utilized to confirm hip impingement and Tönnis grade was used to define pre-OA (Tönnis grade 0-1) and advanced OA (Tönnis grade >2). Safranin O stained sections were used to assess cartilage degeneration using the Mankin score. Immunostaining of IL-1β, MMP-13, ADAMTS-4, type II collagen (COL2), and the NITEGE aggrecan neoepitote was performed to evaluate inflammation and catabolic markers. Quantification of immunopositive cells was performed and one-way analysis of variance with Tukey’s post hoc test was applied to analyze differences between groups. Results: Characteristics of the study participants are presented in Table 1. Cartilage from the impingement zone (head-neck and acetabulum) of hips with early and late FAI showed microscopic osteoarthritic degenerative changes. Compared to control, head-neck cartilage from early and late stage FAI hips highly expressed inflammatory and catabolic markers IL-1β (69.7±18.1, 72.5±13.2 vs 20.2±4.9), MMP-13 (79.6±12.6, 71.4±18.8 vs 25.3±9.5), ADAMTS-4 (83.9±12.2, 82.6±12.5 vs 24.3±11.1), NITEGE (89.7±7.7, 95.7±4.7 vs 39.8±20.5) (p<0.05). Expression for COL2 was similar among groups (93.6±3.9, 92.5±5.8 vs 95.4±6.4, p=0.4892). Finally, percent of immunopositive cells for IL-1β, MMP-13, ADAMTS-4, and ACAN were positively correlated with Mankin score (r=0.52-0.75; p<0.001). The percentage of immunopositive cells present in acetabular cartilage was similar in both early and late FAI (IL-1β: 83.3 ± 24.8, 80.7 ± 15.6, 80.9 ± 26.3, p = 0.9571; MMP-13: 94.3 ± 9.7, 85.2 ± 12.3, 93.3 ± 10.3, p = 0.0653; ADAMTS-4: 98.5 ± 2.3, 98.4 ± 3.4, 99.2 ± 3.0, p = 0.6997, COL2: 99.8 ± 0.7, 99.7 ± 1.1, 98.6 ± 3.6, p = 0.3830). Additionally, inflammatory and catabolic markers were secreted to the ECM (extracellular matrix) in late FAI but not in early FAI. (Figure 1) Synovitis was minimal in early FAI but severe in late FAI. The average synovitis score was lower in early FAI than late FAI (2.5 ± 1.7, 4.4 ± 1.6; p=0.0086). Lower IL-1β expression levels were noted in synovium from early FAI compared to late FAI (p=0.001). Conclusion: Osteoarthritic degenerative changes, inflammation and catabolic markers are evident in the cartilage from the head-neck and acetabulum (impingement zone) in patients with hip FAI morphology during early and late stage disease. In late disease, increase expression of these markers are also observed in the ECM. Severe synovitis, however, was only evident in late stage disease. This study defines joint specific location and timing of inflammation relative to the disease process, suggesting the impingement area is a potential mediator of inflammation and joint degeneration during disease progression.

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Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement

The American Journal of Sports Medicine ◽

10.1177/0363546520935440 ◽

2020 ◽

Vol 48 (10) ◽

pp. 2481-2488

Author(s):

Masahiko Haneda ◽

Muhammad Farooq Rai ◽

Lei Cai ◽

Robert H. Brophy ◽

Regis J. O’Keefe ◽

...

Keyword(s):

Femoroacetabular Impingement ◽

Late Stage ◽

Early Stage ◽

Hip Osteoarthritis ◽

Cartilage Degeneration ◽

Control Group ◽

Acetabular Cartilage ◽

Similar Expression ◽

Related Proteins ◽

Head Neck

Background: The molecular mechanism of how femoroacetabular impingement (FAI) morphology leads to hip osteoarthritis (OA) is yet to be determined. The expression and location of inflammation-related molecules during early- and late-stage FAI have not been previously described. Moreover, the characterization of intra-articular inflammation away from the cam deformity as well as the nature of adjacent synovial tissue have also not been extensively reported. Hypothesis: Early-stage FAI has a similar expression of inflammation-related markers in the head-neck and acetabular cartilage but less synovitis than late-stage FAI. Study Design: Controlled laboratory study. Methods: Head-neck cartilage, acetabular cartilage, and synovial samples were obtained from patients undergoing hip preservation surgery for the treatment of symptomatic cam FAI (early FAI group; n = 15) and advanced OA secondary to cam FAI (late FAI group; n = 15). Samples procured from healthy young adult donors served as the control group (n = 7). Cartilage degeneration was assessed by histology, and the expression of inflammation-related proteins (interleukin–1 beta [IL-1β], matrix metalloproteinase–13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motifs–4 [ADAMTS-4], type II collagen [COL2], and aggrecan neoepitope [NITEGE]) was measured by immunostaining. Synovial samples in the early and late FAI groups were examined for synovitis and the expression of IL-1β. Results: Head-neck cartilage in the early FAI group showed significantly more degeneration than the control group and an increased expression of inflammation-related proteins (IL-1β: 69.7% ± 18.1% vs 20.2% ± 4.9%, respectively; MMP-13: 79.6% ± 12.6% vs 25.3% ± 9.5%; ADAMTS-4: 83.9% ± 12.2% vs 24.3% ± 11.1%; NITEGE: 89.7% ± 7.7% vs 39.8% ± 20.5%) ( P < .001). Head-neck and acetabular cartilage in the early and late FAI groups showed a similar degree of degeneration. Moreover, a similar expression of inflammation-related proteins was observed between the early and late FAI groups for head-neck cartilage (IL-1β: 69.7% ± 18.1% vs 72.5% ± 13.2%; MMP-13: 79.6% ± 12.6% vs 71.4% ± 18.8%; ADAMTS-4: 83.9% ± 12.2% vs 82.6% ± 12.5%; COL2: 93.6% ± 3.9% vs 92.5% ± 5.8%; NITEGE: 89.7% ± 7.7% vs 95.7% ± 4.7%) and acetabular cartilage (IL-1β: 83.3% ± 24.8% vs 80.7% ± 15.6%; MMP-13: 94.3% ± 9.7% vs 85.2% ± 12.3%; ADAMTS-4: 98.5% ± 2.3% vs 98.4% ± 3.4%; COL2: 99.8% ± 0.7% vs 99.7% ± 1.1%; NITEGE: 96.7% ± 6.7% vs 99.2% ± 2.2%). In contrast, synovitis was minimal with a low expression of IL-1β in the early FAI group compared with the late FAI group. Conclusion: Hip cartilage exhibited an OA phenotype in patients with early-stage FAI, similar to what was observed in hip OA secondary to FAI. Severe synovitis was only evident with late-stage FAI. Clinical Relevance: This study supports the concept that early hip impingement is associated with cartilage degeneration and catabolism.

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Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism

AIDS ◽

10.1097/qad.0b013e328359a89d ◽

2012 ◽

Vol 26 (18) ◽

pp. 2275-2284 ◽

Cited By ~ 12

Author(s):

José M. Marcelino ◽

Pedro Borrego ◽

Charlotta Nilsson ◽

Carlos Família ◽

Helena Barroso ◽

...

Keyword(s):

Late Stage ◽

Antibody Neutralization ◽

Stage Disease ◽

Late Stage Disease

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Receipt of Screening Mammography by Insured Women Diagnosed With Breast Cancer and Impact on Outcomes

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.7801 ◽

2021 ◽

Author(s):

Marissa B. Lawson ◽

Christoph I. Lee ◽

Daniel S. Hippe ◽

Shasank Chennupati ◽

Catherine R. Fedorenko ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Late Stage ◽

Breast Cancer Diagnosis ◽

Screening Mammography ◽

Socioeconomic Deprivation ◽

Tumor Characteristics ◽

Stage Disease ◽

Increased Risk ◽

Late Stage Disease

Background: The purpose of this study was to determine factors associated with receipt of screening mammography by insured women before breast cancer diagnosis, and subsequent outcomes. Patients and Methods: Using claims data from commercial and federal payers linked to a regional SEER registry, we identified women diagnosed with breast cancer from 2007 to 2017 and determined receipt of screening mammography within 1 year before diagnosis. We obtained patient and tumor characteristics from the SEER registry and assigned each woman a socioeconomic deprivation score based on residential address. Multivariable logistic regression models were used to evaluate associations of patient and tumor characteristics with late-stage disease and nonreceipt of mammography. We used multivariable Cox proportional hazards models to identify predictors of subsequent mortality. Results: Among 7,047 women, 69% (n=4,853) received screening mammography before breast cancer diagnosis. Compared with women who received mammography, those with no mammography had a higher proportion of late-stage disease (34% vs 10%) and higher 5-year mortality (18% vs 6%). In multivariable modeling, late-stage disease was most associated with nonreceipt of mammography (odds ratio [OR], 4.35; 95% CI, 3.80–4.98). The Cox model indicated that nonreceipt of mammography predicted increased risk of mortality (hazard ratio [HR], 2.00; 95% CI, 1.64–2.43), independent of late-stage disease at diagnosis (HR, 5.00; 95% CI, 4.10–6.10), Charlson comorbidity index score ≥1 (HR, 2.75; 95% CI, 2.26–3.34), and negative estrogen receptor/progesterone receptor status (HR, 2.09; 95% CI, 1.67–2.61). Nonreceipt of mammography was associated with younger age (40–49 vs 50–59 years; OR, 1.69; 95% CI, 1.45–1.96) and increased socioeconomic deprivation (OR, 1.05 per decile increase; 95% CI, 1.03–1.07). Conclusions: In a cohort of insured women diagnosed with breast cancer, nonreceipt of screening mammography was significantly associated with late-stage disease and mortality, suggesting that interventions to further increase uptake of screening mammography may improve breast cancer outcomes.

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Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

Journal of Hepatology ◽

10.1016/s0168-8278(02)00060-0 ◽

2002 ◽

Vol 36 (6) ◽

pp. 805-811 ◽

Cited By ~ 131

Author(s):

Sanjiv K. Jain ◽

Philip W. Pemberton ◽

Alexander Smith ◽

Raymond F.T. McMahon ◽

Peter C. Burrows ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Late Stage ◽

Stage Disease ◽

Late Stage Disease

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Natural alteration of HIV-1 co-receptor tropism by contemporaneous HIV-2 infection

10.1101/410456 ◽

2018 ◽

Author(s):

Joakim Esbjörnsson ◽

Fredrik Månsson ◽

Hans Norrgren ◽

Sarah L. Rowland-Jones

Keyword(s):

Late Stage ◽

Stage Disease ◽

Late Stage Disease ◽

Underlying Mechanisms ◽

Disease Understanding ◽

Hiv 1 ◽

The Way

In this study, we show that the pathogenic HIV-1 CXCR4-tropism is more common in HIV-1 single (79%) than in HIV-1 and HIV-2 dual-infected individuals (35%), suggesting that contemporaneous HIV-2 infection can affect HIV-1 co-receptor tropism in late-stage disease. Understanding the underlying mechanisms responsible for this natural alteration by HIV-2 could pave the way towards a deeper understanding of the AIDS pathogenesis.

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Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz259 ◽

2019 ◽

Vol 220 (7) ◽

pp. 1172-1177 ◽

Cited By ~ 6

Author(s):

Mark J Siedner ◽

Mwebesa Bosco Bwana ◽

Stephen Asiimwe ◽

Gideon Amanyire ◽

Nicholas Musinguzi ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Late Stage ◽

Sub Saharan Africa ◽

Cd4 T Cell ◽

Disease Stage ◽

Stage Disease ◽

Late Stage Disease ◽

Cd4 T Cell Count

Abstract Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count <200/µL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

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Complete remission of cancer in late-stage disease by radiation and transfer of allogeneic MHC-matched immune T cells: lessons from GvL studies in animals

Cancer Immunology Immunotherapy ◽

10.1007/s00262-014-1530-2 ◽

2014 ◽

Vol 63 (6) ◽

pp. 535-543 ◽

Cited By ~ 6

Author(s):

Volker Schirrmacher

Keyword(s):

T Cells ◽

Complete Remission ◽

Late Stage ◽

Stage Disease ◽

Late Stage Disease

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The management of sinogenic orbital complications

The Journal of Laryngology & Otology ◽

10.1017/s0022215100129974 ◽

1995 ◽

Vol 109 (4) ◽

pp. 300-303 ◽

Cited By ~ 15

Author(s):

Bharath Singh

Keyword(s):

Conservative Treatment ◽

Eye Movement ◽

Late Stage ◽

Stage Disease ◽

Intravenous Antibiotics ◽

Late Stage Disease ◽

Group 3 ◽

Group 2 ◽

Orbital Complications ◽

Group 1

AbstractThe place of conservative treatment in sinogenic orbital complications has not been fully explained in the literature. The question that remains unresolved is – at which stage of the disease is surgery indicated?A study was undertaken in 240 patients with sinogenic orbital complications, to determine this. The patients were divided into three groups according to the stage of the disease as determined clinically: Group 1 (52 patients) with early stage disease, as detected by cellulitis only; Group 2 (76 patients) with intermediate stage, as detected by periorbital cellulitis and proptosis, but with full range of eye movement and unaltered vision: Group 3 (122 patients) with late stage disease, as detected by periorbital cellulitis and gross proptosis. with limitation of eye movement and altered vision.Group I and Group 2 patients were treated conservatively, with intravenous antibiotics and antral lavage. Group 3 patients were treated with intravenous antibiotics and surgery. External frontoethmoidectomy was performed in 31 (bilateral in two), ethmoidectomy in 91 (bilateral in five), sphenoidectomy in 15 and bilateral antral washout in all (122 patients). There was 100 per cent success with conservative treatment in Group 1 patients, whilst in Group 2 there was 98.6 per cent failure. The 75 patients in whom conservative treatment failed were successfully treated with surgery: frontoethmoidectomy was performed in 66 and ethmoidectomy in nine. In Group 3 patients, 100 per cent success was achieved with intravenous antibiotics and surgery.Sinogenic orbital complications can be treated conservatively and surgically, depending on the stage of the disease on presentation. Conservative treatment is only suitable for early complications, i.e. patients with periorbital cellulitis only. For disease beyond this stage i.e. intermediate and late stage disease, surgery is the treatment of choice.

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