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

2020 ◽  
Vol 48 (10) ◽  
pp. 2481-2488
Author(s):  
Masahiko Haneda ◽  
Muhammad Farooq Rai ◽  
Lei Cai ◽  
Robert H. Brophy ◽  
Regis J. O’Keefe ◽  
...  

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.

2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0034
Author(s):  
Masahiko Haneda ◽  
John Clohisy ◽  
M. Farooq Rai ◽  
Regis O’Keefe ◽  
Robert Brophy ◽  
...  

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.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanying Gao ◽  
Ruiqi Wu ◽  
Rongge Liu ◽  
Jianquan Wang ◽  
Yingfang Ao ◽  
...  

Abstract Background Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI. Methods Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters. Results In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05). Conclusions Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.


2020 ◽  
Vol 28 (3) ◽  
pp. 230949902095057
Author(s):  
Mayumi Sonekatsu ◽  
Motoki Sonohata ◽  
Takao Inoue ◽  
Hidefumi Honke ◽  
Masaru Kitajima ◽  
...  

Purpose: There are many radiographic parameters to evaluate developmental dysplasia of the hip joint (DDH); however, the priority between the parameters is unclear. We evaluated the priority of radiographic parameters in DDH. Methods: We retrospectively reviewed the radiographs of 82 consecutive patients aged above 85 years without hip osteoarthritis (OA; no osteoarthritis (NO) group), and 28 patients with early stage hip OA were set as the control group (OA group). We used the linear discriminant analysis (LDA) to consider the priority of the following parameters: acetabular roof obliquity (ARO), center-edge (CE) angle, Sharp angle, acetabular head index (AHI), and acetabular depth ratio (ADR). Results: The LDA of five different parameters revealed that the NO and OA groups could be almost distinguished with 83.6% accuracy ( p < 0.0001, Wilks’ lambda test). The standardized scoring coefficients were as follows: ARO, −0.23; CE, −0.43; Sharp, −0.29; AHI, 0.97; and ADR, 0.11. The AHI was particularly noticeable in the NO group. Conclusion: Dissociation of the AHI in the OA group was significantly higher than that of the other parameters in the OA group compared to the parameters in the NO group. A small AHI may be a risk parameter for hip OA due to DDH.


2021 ◽  
Author(s):  
Christopher Hane ◽  
Stephan Dunning ◽  
Jeffrey McPheeters ◽  
David Mosely ◽  
Jennifer St. Clair Russell ◽  
...  

Abstract Background and objectives Patients with undiagnosed CKD are at increased risk of suboptimal dialysis initiation and therefore reduced access to home dialysis and transplantation as well as poor outcomes. Improved understanding of how patients remain undiagnosed is important to determine better intervention strategies. Design, setting, participants, and measurements A retrospective, matched, case-control analysis of 1,535,053 patients was performed to identify factors differentiating 4 patient types: unrecognized late-stage CKD, recognized late-stage CKD, early-stage CKD and a control group without CKD. The sample included patients with commercial insurance, Medicare Advantage, and Medicare fee-for service coverage. Patient demographics, comorbidities, health care utilization, and prescription use were analyzed using random forests to determine the most salient features discriminating the types. Models were built using all four types, as well as pairwise for each type versus the unrecognized late-stage type. Results Area under the curve for the three pairwise models (unrecognized late-stage vs recognized late-stage; unrecognized late-stage vs early-stage; unrecognized late-stage vs no CKD) were 82%, 68% and 82%. Conclusions The lower performance of the unrecognized late-stage vs early-stage model indicates a greater similarity of these two patient groups. The unrecognized late-stage CKD group is not simply avoiding or unable to get care in a manner distinguishable from the early-stage group. New outreach for CKD to undiagnosed or undetected, insured patients should look more closely at patient sets that are like diagnosed early-stage CKD patients.


Cartilage ◽  
2020 ◽  
pp. 194760352094124
Author(s):  
Florian Schmaranzer ◽  
Pascal C. Haefeli ◽  
Emanuel F. Liechti ◽  
Markus S. Hanke ◽  
Moritz Tannast ◽  
...  

Objective To assess whether subchondral drilling of acetabular cartilage flaps during femoroacetabular impingement (FAI) surgery improves (1) acetabular dGEMRIC indices and (2) morphologic magnetic resonance imaging (MRI) scores, compared with hips in which no additional treatment of cartilage lesions had been performed; and (3) whether global dGEMRIC indices and MRI scores correlate. Design Prospective cohort study of consecutive patients with symptomatic FAI treated with open surgery between 2000 and 2007. Patients with subchondral drilling of acetabular cartilage flaps were allocated to the study group, those without drilling to the control group. All patients underwent indirect 3-T MR arthrography to assess cartilage quality by dGEMRIC indices and a semiquantitative morphologic MRI score at minimum 5 years after surgery. dGEMRIC indices and morphologic MRI scores were compared between and among groups using analysis of covariance/paired t tests. Results No significant difference was found between the global dGEMRIC indices of the study group (449 ± 147 ms, 95% CI 432-466 ms) and the control group (428 ± 143 ms, 95% CI 416-442 ms; P = 0.235). In regions with cartilage flaps, the study group showed higher dGEMRIC indices (472 ± 160 ms, 95% CI 433-510 ms) compared with the control group (390 ± 122 ms, 95% CI 367-413 ms; P < 0.001). No significant differences were found for the morphologic MRI scores. A strong inversely linear correlation between the dGEMRIC indices and the morphologic MRI scores ( r = −0.727, P < 0.001) was observed. Conclusions Treatment of acetabular cartilage flaps with subchondral drilling leads to better cartilage quality in regions with cartilage flaps at minimum 5 years of follow-up.


2020 ◽  
Vol 28 (2) ◽  
pp. 230949902092416
Author(s):  
Takehito Hananouchi ◽  
Stephen Kenji Aoki

The morphological characteristics associated with a diagnosis of femoroacetabular impingement (FAI) observed on plain radiographs can also be seen in subjects without hip joint symptoms. Therefore, the purpose of this study was to investigate whether sclerotic lesions on femoral head–neck junction (FHNJ) could be used as a supplemental diagnostic feature. A total of 128 hips from 119 patients (43 male and 76 female) diagnosed with FAI and 24 hips from 21 patients (2 male and 19 female) with other hip pathologies as control were compared in this study. Using standing frog-leg plain radiographs, the prevalence of sclerotic lesions on the FHNJ was established. Additionally, the pixel intensity (PI) of the sclerotic lesions between the FAI and the control groups were quantitatively compared. Sclerotic lesions were present in 96.1% of FAI hips (123 of 128) and only 37.5% of control hips (9 of 24) ( p < 0.05). The ratio of PI in the FAI group was significantly higher (approximately 10%) than in the control group ( p < 0.05). The evaluation of sclerotic lesions may be used as a supplement to aid in the diagnosis of FAI.


2021 ◽  
Vol 2 (11) ◽  
pp. 988-996
Author(s):  
Maryam Mohtajeb ◽  
Jolanda Cibere ◽  
Michelle Mony ◽  
Honglin Zhang ◽  
Emily Sullivan ◽  
...  

Aims Cam and pincer morphologies are potential precursors to hip osteoarthritis and important contributors to non-arthritic hip pain. However, only some hips with these pathomorphologies develop symptoms and joint degeneration, and it is not clear why. Anterior impingement between the femoral head-neck contour and acetabular rim in positions of hip flexion combined with rotation is a proposed pathomechanism in these hips, but this has not been studied in active postures. Our aim was to assess the anterior impingement pathomechanism in both active and passive postures with high hip flexion that are thought to provoke impingement. Methods We recruited nine participants with cam and/or pincer morphologies and with pain, 13 participants with cam and/or pincer morphologies and without pain, and 11 controls from a population-based cohort. We scanned hips in active squatting and passive sitting flexion, adduction, and internal rotation using open MRI and quantified anterior femoroacetabular clearance using the β angle. Results In squatting, we found significantly decreased anterior femoroacetabular clearance in painful hips with cam and/or pincer morphologies (mean -11.3° (SD 19.2°)) compared to pain-free hips with cam and/or pincer morphologies (mean 8.5° (SD 14.6°); p = 0.022) and controls (mean 18.6° (SD 8.5°); p < 0.001). In sitting flexion, adduction, and internal rotation, we found significantly decreased anterior clearance in both painful (mean -15.2° (SD 15.3°); p = 0.002) and painfree hips (mean -4.7° (SD 13°); p = 0.010) with cam and/pincer morphologies compared to the controls (mean 7.1° (SD 5.9°)). Conclusion Our results support the anterior femoroacetabular impingement pathomechanism in hips with cam and/or pincer morphologies and highlight the effect of posture on this pathomechanism. Cite this article: Bone Jt Open 2021;2(11):988–996.


2020 ◽  
Author(s):  
Minhao Yu ◽  
Yalin Cheng

Abstract Purpose This study analyzed the morbidity and mortality associated with non-small cell lung cancer (NSCLC) and evaluated treatment strategies for it in a low-risk area of COVID-19 in China. Materials and methods: We selected patients admitted to Sichuan Science City Hospital from September 2019 to February 2020 and divided them into experimental and control groups. The treatment strategy was evaluated by patients’ prognosis. Results: 9,010 patients were hospitalized. The total morbidity was 0.699%, of which 0.504% was observed in the control group and 0.991% in the experimental group (P=0.024). The total mortality was 0.999/103, of which 0.630/103 was observed in the control group and 1.413/103 in the experimental group (P=0.322). Therapy discontinuation and cancer progression in the experimental group were significantly higher than the control group (P<0.001, P=0.007). The treatment methods and prognosis were not significantly different for early-stage patients between the two groups. Late-stage patients in the experimental group experienced significantly lower percentages of non-surgical treatments (P<0.001), higher percentages of discontinued therapies (P<0.001), lower percentages for prognosis of wellness (P<0.001), and higher percentages of cancer progression (P<0.001) than the control group. Conclusion: NSCLC exhibited significantly higher morbidities during the COVID-19 pandemic. The mortality in the experimental group was slightly higher than the control group, while the difference in cancer progression was significant. It is feasible to perform surgery for early-stage NSCLC patients, and treatment should not be suspended for late-stage patients in regions with low-risk for COVID-19 infection.


Cartilage ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 118-126 ◽  
Author(s):  
Tobias Hesper ◽  
Christina Neugroda ◽  
Christoph Schleich ◽  
Gerald Antoch ◽  
Harish Hosalkar ◽  
...  

Objective To evaluate the diagnostic accuracy of T2*-mapping for detecting acetabular cartilage damage in patients with symptomatic femoroacetabular impingement (FAI). Design A total of 29 patients (17 females, 12 males, mean age 35.6 ± 12.8 years, mean body mass index 25.1 ± 4.1 kg/m2, 16 right hips) with symptomatic FAI underwent T2* MRI and subsequent hip arthroscopy. T2* values were obtained by region of interest analysis in seven radially reformatted planes around the femoral neck (anterior, anterior-superior, superior-anterior, superior, superior-posterior, posterior-superior, posterior). Intraoperatively, a modified Outerbridge classification was used for assessment of the cartilage status in each region. T2* values and intraoperative data were compared, and sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV) as well as the correlation between T2*-mapping and intraoperative findings, were determined. The mean time interval between MRI and arthroscopy was 65.7 ± 48.0 days. Results Significantly higher T2* values were noted in arthroscopically normal evaluated cartilage than in regions with cartilage degeneration (mean T2* 25.6 ± 4.7 ms vs. 19.9 ± 4.5 ms; P < 0.001). With the intraoperative findings as a reference, sensitivity, specificity, NPV and PPV were 83.5%, 67.7%, 78.4% and 74.4%, respectively. The correlation between T2*-mapping and intraoperative cartilage status was moderate (ρ = −0.557; P < 0.001). Conclusions T2*-mapping enabled analysis of acetabular cartilage with appropriate correlation with intraoperative findings and promising results for sensitivity, specificity, PPV, and NPV in this cohort. Our results emphasize the value of T2*-mapping for the diagnosis of hip joint cartilage pathologies in symptomatic FAI.


Author(s):  
Tian Xie ◽  
Chengnan Chu ◽  
Shilong Sun ◽  
Xinyu Wang ◽  
Zehua Duan ◽  
...  

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detail mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular trap (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy based on their effects on NETs formation in CLP model. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. The in vitro study showed that imipenem and ceftriaxone had opposite effects on NETs formation in activated neutrophils. De-escalation therapy resulted in an evaluated MPO-DNA during early stage and decreased MPO-DNA during late stage, which exerted the reverse effects in escalation therapy sepsis animal model. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAseI during early stage of sepsis (p<0.01). Histopathological analysis showed decreased injury in lung, liver and intestine in de-escalation therapy compared with escalation therapy (p<0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p<0.01), however, no significant difference was found between de-escalation and escalation group (p=0.051). We demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage and inhibiting NETs formation in the late stage of sepsis.


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